Download PDF

Clinical Trial Results:
A Phase 1/2 Combined Dose Ranging and Randomised, Open-label, Comparative Study of the Efficacy and Safety of Plerixafor in Addition to Standard Regimens for Mobilisation of Haematopoietic Stem Cells into Peripheral Blood, and Subsequent Collection by Apheresis, Versus Standard Mobilisation Regimens Alone in Paediatric Patients, Aged 1 to <18 Years, with Solid Tumours Eligible for Autologous Transplants

Summary
EudraCT number	2010-019340-40
Trial protocol	GB DE IT ES BE HU CZ NL DK PL Outside EU/EEA
Global end of trial date	09 May 2017

Results information
Results version number	v1(current)
This version publication date	24 Nov 2017
First version publication date	24 Nov 2017
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

MOZ15609-DFI12860

ISRCTN number

US NCT number

NCT01288573

WHO universal trial number (UTN)

Other trial identifiers

Study name: MOZAIC

Sponsor organisation name

Genzyme Corporation

Sponsor organisation address

500 Kendall Street , Cambridge, MA, United States, 02142

Public contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Scientific contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000174-PIP01-07

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

06 Jun 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 May 2017

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study is to confirm the appropriate dose and efficacy, and to characterise the safety, pharmacokinetics and pharmacodynamics of plerixafor across age and size in paediatric cancer subjects when given in addition to standard mobilisation of hematopoietic stem cells (HSCs) into peripheral blood.

Protection of trial subjects

The study was conducted by investigators experienced in the treatment of paediatric patients. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anaesthesia may have been used to minimize distress and discomfort.

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Feb 2011

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

2 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 3

Country: Number of subjects enrolled

Poland: 2

Country: Number of subjects enrolled

Spain: 6

Country: Number of subjects enrolled

United Kingdom: 7

Country: Number of subjects enrolled

Belgium: 1

Country: Number of subjects enrolled

Czech Republic: 10

Country: Number of subjects enrolled

France: 2

Country: Number of subjects enrolled

Germany: 12

Country: Number of subjects enrolled

Hungary: 2

Country: Number of subjects enrolled

Italy: 22

Country: Number of subjects enrolled

Israel: 5

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The study was conducted in 11 countries between 18 February 2011 and 09 May 2017. A total of 72 subjects were enrolled and treated in the study. The study was conducted in 2 stages. Stage 1 was the dose escalation study and stage 2 was the comparative study using the appropriate dosing regimen identified in Stage 1.

Screening details

During Stage 1, 27 subjects assigned to plerixafor dose group according to their age & progress with dose escalation within that age group. During Stage 2, 45 subjects randomized in 2:1 ratio to receive either plerixafor + standard mobilization or standard mobilization alone.Standard mobilization was G-CSF ± chemotherapy per site standard practice.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Stage 1: Plerixafor 160 mcg /kg: 2-<6 years

Arm description

Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Plerixafor

Investigational medicinal product code

GZ316455/ SAR316455

Other name

Mozobil®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Plerixafor 160 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

Investigational medicinal product name

Non-IMP: Granulocyte Colony-Stimulating Factor (G-CSF)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy as per site standard practice.

Stage 1: Plerixafor 240 mcg /kg: 2-<6 years

Arm description

Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Plerixafor

Investigational medicinal product code

GZ316455/ SAR316455

Other name

Mozobil®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Plerixafor 240 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

Investigational medicinal product name

Non-IMP: G-CSF

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

Stage 1: Plerixafor 320 mcg /kg: 2-<6 years

Arm description

Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Plerixafor

Investigational medicinal product code

GZ316455/ SAR316455

Other name

Mozobil®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Plerixafor 320 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

Investigational medicinal product name

Non-IMP: G-CSF

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

Stage 1: Plerixafor 160 mcg /kg: 6-<12 years

Arm description

Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Plerixafor

Investigational medicinal product code

GZ316455/ SAR316455

Other name

Mozobil®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Plerixafor 160 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

Investigational medicinal product name

Non IMP: G-CSF

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

Stage 1: Plerixafor 240 mcg /kg: 6-<12 years

Arm description

Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Plerixafor

Investigational medicinal product code

GZ316455/ SAR316455

Other name

Mozobil®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Plerixafor 240 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

Investigational medicinal product name

Non-IMP: G-CSF

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

Stage 1: Plerixafor 320 mcg /kg: 6-<12 years

Arm description

Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Plerixafor

Investigational medicinal product code

GZ316455/ SAR316455

Other name

Mozobil®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Plerixafor 320 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

Investigational medicinal product name

Non-IMP: G-CSF

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

Stage 1: Plerixafor 160 mcg /kg: 12-<18 years

Arm description

Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Plerixafor

Investigational medicinal product code

GZ316455/ SAR316455

Other name

Mozobil®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Plerixafor 160 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

Investigational medicinal product name

Non IMP: G-CSF

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

Stage 1: Plerixafor 240 mcg/kg: 12-<18 years

Arm description

Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Plerixafor

Investigational medicinal product code

GZ316455/ SAR316455

Other name

Mozobil®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Plerixafor 240 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

Investigational medicinal product name

Non-IMP: G-CSF

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

Stage 1: Plerixafor 320 mcg/kg: 12-<18 years

Arm description

Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Plerixafor

Investigational medicinal product code

GZ316455/ SAR316455

Other name

Mozobil®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Plerixafor 320 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

Investigational medicinal product name

Non-IMP: G-CSF

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

Stage 2: Standard Mobilization Regimen - G-CSF

Arm description

Subjects started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Treatment G-CSF (alone or in combination with chemotherapy) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Non IMP: G-CSF

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF

Arm description

Subjects started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Arm type

Experimental

Investigational medicinal product name

Plerixafor

Investigational medicinal product code

GZ316455/ SAR316455

Other name

Mozobil®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Plerixafor 240 mcg/kg was administered 8 to 12 hours prior to the initiation of apheresis.

Investigational medicinal product name

Non-IMP: G-CSF

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

Number of subjects in period 1	Stage 1: Plerixafor 160 mcg /kg: 2-<6 years	Stage 1: Plerixafor 240 mcg /kg: 2-<6 years	Stage 1: Plerixafor 320 mcg /kg: 2-<6 years	Stage 1: Plerixafor 160 mcg /kg: 6-<12 years	Stage 1: Plerixafor 240 mcg /kg: 6-<12 years	Stage 1: Plerixafor 320 mcg /kg: 6-<12 years	Stage 1: Plerixafor 160 mcg /kg: 12-<18 years	Stage 1: Plerixafor 240 mcg/kg: 12-<18 years	Stage 1: Plerixafor 320 mcg/kg: 12-<18 years	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Started	3	3	3	3	3	3	3	3	3	15	30
Completed	2	2	3	2	3	0	2	2	1	10	25
Not completed	1	1	0	1	0	3	1	1	2	5	5
Consent withdrawn by subject	-	-	-	-	-	-	-	-	-	1	1
Death	-	-	-	1	-	1	-	1	1	3	3
Other than specified	1	-	-	-	-	-	1	-	1	-	1
Lost to follow-up	-	1	-	-	-	1	-	-	-	-	-
Progressive disease	-	-	-	-	-	1	-	-	-	1	-

Baseline characteristics

Top of page

Reporting group title

Stage 1: Plerixafor 160 mcg /kg: 2-<6 years

Reporting group description

Reporting group title

Stage 1: Plerixafor 240 mcg /kg: 2-<6 years

Reporting group description

Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 320 mcg /kg: 2-<6 years

Reporting group description

Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 160 mcg /kg: 6-<12 years

Reporting group description

Reporting group title

Stage 1: Plerixafor 240 mcg /kg: 6-<12 years

Reporting group description

Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 320 mcg /kg: 6-<12 years

Reporting group description

Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 160 mcg /kg: 12-<18 years

Reporting group description

Reporting group title

Stage 1: Plerixafor 240 mcg/kg: 12-<18 years

Reporting group description

Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 320 mcg/kg: 12-<18 years

Reporting group description

Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 2: Standard Mobilization Regimen - G-CSF

Reporting group description

Reporting group title

Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF

Reporting group description

Reporting group values	Stage 1: Plerixafor 160 mcg /kg: 2-<6 years	Stage 1: Plerixafor 240 mcg /kg: 2-<6 years	Stage 1: Plerixafor 320 mcg /kg: 2-<6 years	Stage 1: Plerixafor 160 mcg /kg: 6-<12 years	Stage 1: Plerixafor 240 mcg /kg: 6-<12 years	Stage 1: Plerixafor 320 mcg /kg: 6-<12 years	Stage 1: Plerixafor 160 mcg /kg: 12-<18 years	Stage 1: Plerixafor 240 mcg/kg: 12-<18 years	Stage 1: Plerixafor 320 mcg/kg: 12-<18 years	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF	Total
Number of subjects	3	3	3	3	3	3	3	3	3	15	30	72
Age categorical
Units: Subjects
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	3	1	4
Children (2-<12 years)	3	3	3	3	3	3	0	0	0	10	24	52
Adolescents (12-<18 years)	0	0	0	0	0	0	3	3	3	2	5	16
Gender categorical
Units: Subjects
Female	2	2	3	1	1	1	1	3	2	8	11	35
Male	1	1	0	2	2	2	2	0	1	7	19	37

End points

Top of page

Reporting group title

Stage 1: Plerixafor 160 mcg /kg: 2-<6 years

Reporting group description

Reporting group title

Stage 1: Plerixafor 240 mcg /kg: 2-<6 years

Reporting group description

Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 320 mcg /kg: 2-<6 years

Reporting group description

Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 160 mcg /kg: 6-<12 years

Reporting group description

Reporting group title

Stage 1: Plerixafor 240 mcg /kg: 6-<12 years

Reporting group description

Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 320 mcg /kg: 6-<12 years

Reporting group description

Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 160 mcg /kg: 12-<18 years

Reporting group description

Reporting group title

Stage 1: Plerixafor 240 mcg/kg: 12-<18 years

Reporting group description

Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 320 mcg/kg: 12-<18 years

Reporting group description

Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 2: Standard Mobilization Regimen - G-CSF

Reporting group description

Reporting group title

Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF

Reporting group description

Primary: Stage 2: Percentage of Subjects Achieving At least a Doubling of Peripheral Blood CD34+ Count

Top of page

End point title

Stage 2: Percentage of Subjects Achieving At least a Doubling of Peripheral Blood CD34+ Count ^[1]

End point description

Percentage of subjects who achieved at least a doubling of peripheral blood CD34+ count (known as successful mobilisation) from the morning of the day preceding the first apheresis day to the morning prior to apheresis was reported in this endpoint. For those subjects who did not have the first apheresis as planned, peripheral CD34+ counts from the morning of the day prior to the planned apheresis day and from the morning of the planned apheresis day itself were included in the analysis. Analysis was performed on full analysis set (FAS) which is comprised of all subjects randomized in Stage 2 according to intent-to-treat (ITT) principle (subjects were analysed according to the treatment group allocated by randomization).

End point type

Primary

End point timeframe

From the morning of the day preceding the first apheresis day to the morning prior to apheresis

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	15	30
Units: percentage of subjects
number (confidence interval 95%)	28.6 (8.4 to 58.1)	80 (61.4 to 92.3)

G-CSF alone vs. G-CSF + Plerixafor

Statistical analysis description

The difference of percentage of successful mobilization was relative to standard mobilization alone treatment group. The confidence interval (CI) of the difference is based on the Wald asymptotic CI with continuity correction method.

Comparison groups

Stage 2: Standard Mobilization Regimen - G-CSF v Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0019 ^[2]

Method

Fisher exact

Parameter type

Difference of percentage

Point estimate

51.4

Confidence interval

level

95%

sides

2-sided

lower limit

18.5

upper limit

84.3

Notes
[2] - Threshold level was estimated at 0.05 level.

Secondary: Stage 2: Median Number of Days of Apheresis Required to Reach >=2 *10^6 CD34+ cells/kg

Top of page

End point title

Stage 2: Median Number of Days of Apheresis Required to Reach >=2 *10^6 CD34+ cells/kg ^[3]

End point description

The number of days of apheresis to reach >=2*10^6 CD34+ cells/kg was estimated using the Kaplan-Meier method. A subject was classified as having the event if the cumulative number of CD34+ cells/kg collected reached the target of ≥2*10^6 CD34+ cells/kg. Subjects not reaching target at the end of apheresis period were censored on the last apheresis day (maximum of 5 apheresis in study). Analysis was performed on FAS. Here, 99999 represents data not calculated since majority of subjects reached CD34+ cells target within 1 day.

End point type

Secondary

End point timeframe

Day 1 up to Day 5

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	15	30
Units: Days
median (full range (min-max))	1 (-99999 to 99999)	1 (-99999 to 99999)

No statistical analyses for this end point

Secondary: Stage 2: Yield of CD34+ (*10^6 cells/kg ) Cells for Each Apheresis

Top of page

End point title

Stage 2: Yield of CD34+ (*10^6 cells/kg ) Cells for Each Apheresis ^[4]

End point description

Apheresis commenced on the morning following the day when the peripheral blood (PB) CD34+ count reached the target trigger point minimum of 7 CD34+ cells/mcl. Here, 99999 represented that data was not estimable as none of the evaluable subjects had Day 3 apheresis except for 1 subject in the plerixafor + standard mobilization arm. Analysis was performed on FAS population. Here 'n' signifies number of subjects with available data for specified category.

End point type

Secondary

End point timeframe

Days 1 up to Day 3 following apheresis

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	15	30
Units: cells (*10^6 cells/kg)
arithmetic mean (standard deviation)
Day 1 (n= 14, 29)	17.57 ( 20.79 )	19.44 ( 36.7 )
Day 2 (n = 2, 3)	2.8 ( 3.3 )	0.69 ( 1.07 )
Day 3 (n = 0, 1)	99999 ( 99999 )	0.06 ( 99999 )

No statistical analyses for this end point

Secondary: Stage 2: Total CD34+ Cell Yield

Top of page

End point title

Stage 2: Total CD34+ Cell Yield ^[5]

End point description

The cumulative CD34+ cells/kg yield was calculated by summing the CD34+ yield from each apheresis. Analysis was performed on FAS population. Number of subjects analysed=number of subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Day 1 up to Day 3 following apheresis

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	14	29
Units: cells (*10^6 cells/kg)
arithmetic mean (standard deviation)	17.61 ( 20.76 )	19.44 ( 36.69 )

No statistical analyses for this end point

Secondary: Stage 2: Percentage of Subjects Proceeding to Autologous Transplant

Top of page

End point title

Stage 2: Percentage of Subjects Proceeding to Autologous Transplant ^[6]

End point description

The percentage of subjects proceeding to autologous transplant was calculated using the total number of subjects in the corresponding analysis set as the denominator. Analysis was performed on FAS population.

End point type

Secondary

End point timeframe

Within 6 months of last apheresis (up to maximum duration of 2.5 years)

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	15	30
Units: percentage of subjects
number (confidence interval 95%)	66.7 (38.4 to 88.2)	76.7 (57.7 to 90.1)

No statistical analyses for this end point

Secondary: Stage 2: Percentage of Subjects Successfully Engrafting

Top of page

End point title

Stage 2: Percentage of Subjects Successfully Engrafting ^[7]

End point description

Successful engrafting was when both absolute neutrophil count (ANC) & platelet were successfully engrafted. Percentage of subjects with successful engraftment was calculated using the total number of subjects in each treatment group who received transplantation as the denominator. Analysis was performed on FAS population. Number of subjects analysed= number of subjects who underwent grafting.

End point type

Secondary

End point timeframe

24 months after transplant (up to maximum duration of 2.5 years)

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	10	23
Units: percentage of subjects
number (confidence interval 95%)	100 (69.2 to 100)	100 (85.2 to 100)

No statistical analyses for this end point

Secondary: Stage 2: Percentage of Subjects with Durable Engraftment

Top of page

End point title

Stage 2: Percentage of Subjects with Durable Engraftment ^[8]

End point description

Durable engraftment was defined as subjects with both ANC and platelet engrafted and who remained in the engraftment status at 3, 6, 12, and 24 months post-transplant. The percentage of subjects with durable engraftment at 3, 6, 12, and 24 months post-transplant was calculated using the total number of subjects in each treatment group who received transplant as the denominator. Analysis was performed on FAS population. Number of subjects analysed=number of subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

At 3, 6, 12 and 24 months post-transplant (up to maximum duration of 2.5 years)

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	10	23
Units: percentage of subjects
number (confidence interval 95%)
Month 3	100 (69.2 to 100)	91.3 (72 to 98.9)
Month 6	90 (55.5 to 99.7)	87 (66.4 to 97.2)
Month 12	80 (44.4 to 97.5)	87 (66.4 to 97.2)
Month 24	80 (44.4 to 97.5)	82.6 (61.2 to 95)

No statistical analyses for this end point

Secondary: Stage 1 and Stage 2: Overview of Safety

Top of page

End point title

Stage 1 and Stage 2: Overview of Safety

End point description

Any untoward medical occurrence in a subject who received investigational medicinal product was considered an AE regardless of causal relationship with this treatment. Treatment-Emergent Adverse Events (TEAEs): AEs that developed/worsened/became serious during from the date of enrollment until 30 days after the last dose of subject’s study mobilization regimen/until the 1st dose of next anticancer therapy or pre-transplant myeloablative therapy, whichever occurred first. Serious AE (SAE):any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. Any TEAE included both serious & non-serious AEs. Safety set was defined as all subjects who received at least one dose of study drug.

End point type

Secondary

End point timeframe

From baseline up to the follow up visit (up to 6.2 years)

End point values	Stage 1: Plerixafor 160 mcg /kg: 2-<6 years	Stage 1: Plerixafor 240 mcg /kg: 2-<6 years	Stage 1: Plerixafor 320 mcg /kg: 2-<6 years	Stage 1: Plerixafor 160 mcg /kg: 6-<12 years	Stage 1: Plerixafor 240 mcg /kg: 6-<12 years	Stage 1: Plerixafor 320 mcg /kg: 6-<12 years	Stage 1: Plerixafor 160 mcg /kg: 12-<18 years	Stage 1: Plerixafor 240 mcg/kg: 12-<18 years	Stage 1: Plerixafor 320 mcg/kg: 12-<18 years	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	3	3	3	3	3	3	3	3	3	15	30
Units: percentage of subjects
number (not applicable)
Any TEAE	67	33	33	67	67	67	100	33	67	66.7	76.7
Any treatment-emergent SAE	33.33	0	0	66.67	0	33.33	66.67	0	33.33	26.7	30

No statistical analyses for this end point

Secondary: Stage 2: Percentage of Subjects Who Had Hospitalization

Top of page

End point title

Stage 2: Percentage of Subjects Who Had Hospitalization ^[9]

End point description

Analysis was performed on safety set for stage 2 which included all randomized subjects who received at least one study dose (either plerixafor or standard mobilization) in Stage 2. Subjects from Stage 2 were to be analysed for safety according to the treatment they actually received.

End point type

Secondary

End point timeframe

From randomisation in stage 2 until the end of study (up to maximum duration of 2.5 years)

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	15	30
Units: percentage of subjects
number (not applicable)	86.7	90

No statistical analyses for this end point

Secondary: Stage 2: Percentage of Subjects With Tumor Cell Mobilisation Positive in Peripheral Blood

Top of page

End point title

Stage 2: Percentage of Subjects With Tumor Cell Mobilisation Positive in Peripheral Blood ^[10]

End point description

Tumour cell mobilisation was evaluated by assessment of blood samples for the presence of tumour cells in peripheral blood. Blood samples were collected on the morning of the day preceding the first apheresis day and in the morning prior to G-CSF administration on the first apheresis day itself, as well as in apheresis product after first, second and third apheresis prior to cryopreservation in subjects with neuroblastoma, Ewing’s sarcoma and alveolar rhabdomyosarcoma. Analysis was performed on safety set for stage-2. Here 'n' signifies number of subjects with available data for specified categories for each arm respectively.

End point type

Secondary

End point timeframe

On morning at Day prior to first planned apheresis, morning of first planned apheresis day, first apheresis, second apheresis, third apheresis additional apheresis days (maximum of 5 apheresis) (up to maximum duration of 2.5 years)

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	15	30
Units: percentage of subjects
number (not applicable)
on morning prior to 1st apheresis(n=9, 20)	11.1	0
on morning of 1st apheresis (n=9, 21)	0	0
at 1st apheresis (n=10, 20)	10	5
at 2nd apheresis (n=2, 2)	100	0
at 3rd apheresis (n= 0, 1)	0	0

No statistical analyses for this end point

Secondary: Stage 2: Post-Transplant Relapse Rate

Top of page

End point title

Stage 2: Post-Transplant Relapse Rate ^[11]

End point description

Relapse rate was defined as the percentage of subjects with relapse at 3, 6, 12, and 24 months post-transplant. It was summarized using Kaplan-Meier methods for subjects who received transplant. Time to relapse for subjects who received transplant was defined as the time interval from the date of transplant to the date of first recorded recurrent or progressive disease. Subjects with no recurrent or progressive disease recorded were censored at their last visit. The start date was the date of transplant. Analysis was performed on safety set for stage 2. Number of subjects analysed=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

At month 3, 6, 12, and 24 after transplant (up to a maximum duration of 2.5 years)

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	10	23
Units: Percentage of subjects
number (confidence interval 95%)
Month 3 post-transplant	0.1 (0.015 to 0.527)	0.087 (0.022 to 0.305)
Month 6 post-transplant	0.1 (0.015 to 0.527)	0.087 (0.022 to 0.305)
Month 12 post-transplant	0.1 (0.015 to 0.527)	0.13 (0.044 to 0.352)
Month 24 post-transplant	0.55 (0.266 to 0.873)	0.304 (0.158 to 0.534)

No statistical analyses for this end point

Secondary: Stage 2: Post-Apheresis Relapse Rate

Top of page

End point title

Stage 2: Post-Apheresis Relapse Rate ^[12]

End point description

Relapse rate was defined as the percentage of subjects with relapse at 3, 6, 12, and 24 months post-apheresis. It was summarized using Kaplan-Meier methods for subjects who had apheresis. Time to relapse for subjects who received transplant or not was defined as time interval from the date of last apheresis to the date of the recorded recurrent or progressive disease. Subjects with no recurrent or progressive disease was censored at the last visit. The start date was the date of last apheresis. Analysis was performed on safety set for stage 2. 99999 represents data not calculated as very low number of subject had event (relapse).

End point type

Secondary

End point timeframe

At month 3, 6, 12, and 24 after apheresis (up to maximum duration of 2.5 years)

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	15	30
Units: percentage of subjects
number (confidence interval 95%)
Month 3 post-apheresis	0.071 (0.01 to 0.409)	0 (-99999 to 99999)
Month 6 post-apheresis	0.071 (0.01 to 0.409)	0.036 (0.005 to 0.228)
Month 12 post-apheresis	0.071 (0.01 to 0.409)	0.071 (0.018 to 0.257)
Month 24 post-apheresis	0.357 (0.167 to 0.657)	0.253 (0.129 to 0.459)

No statistical analyses for this end point

Secondary: Stage 2: Percentage of Subjects With Secondary Malignancies

Top of page

End point title

Stage 2: Percentage of Subjects With Secondary Malignancies ^[13]

End point description

The occurrence of secondary malignancies during the 24 months after the last planned transplant performed in the 6-month period after last study apheresis (or 24 months after last dose of study mobilisation treatment for subjects who did not undergo transplant within 6 months after last study apheresis) was recorded for all subjects. Analysis was performed on safety set for stage 2. Here, 99999 represents data not calculated as no subject in both arms had any secondary malignancy.

End point type

Secondary

End point timeframe

Up to 24 months post transplant period (up to a maximum duration of 2.5 years)

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	15	30
Units: percentage of subjects
number (not applicable)	99999	99999

No statistical analyses for this end point

Secondary: Stage 2: Percentage of Subjects with Primary Graft Failure

Top of page

End point title

Stage 2: Percentage of Subjects with Primary Graft Failure ^[14]

End point description

Primary graft failure was defined by the criteria below in the absence of evidence of other causes such as progressive cancer, renal failure, chronic bleeding, severe infection, drug induced cytopaenias, or development of new haematological problems (nutritional or otherwise). Primary neutrophil graft failure was defined as the failure to achieve a sustained ANC of >=0.5*10^9/L (defined by 3 consecutive laboratory values on 3 different days) or >=1.0*10^9/L for 1 day within 30 days post-transplant. Primary platelet graft failure was defined as the failure to achieve a sustained platelet count >=20*10^9/L (defined by at least 3 consecutive platelet laboratory values obtained over at least 7 days without transfusion) within 100 days post-transplant. Analysis was performed on safety set for stage 2. Number of subjects analysed=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to 100 days post-transplant or until disease recurrence or progression whichever occurred first (up to a maximum duration of 2.5 years)

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	10	23
Units: percentage of subjects
number (not applicable)
Primary neutrophil graft failure	0	0
Primary platelet graft failure	0	4.3

No statistical analyses for this end point

Secondary: Stage 2: Percentage of Subjects With Secondary Graft Failure

Top of page

End point title

Stage 2: Percentage of Subjects With Secondary Graft Failure ^[15]

End point description

Secondary graft failure was defined as confirmation of one of the following in the absence of evidence of other causes such as recurrence or progression of cancer, renal failure, chronic bleeding, severe infection, drug-induced cytopaenias, or development of new haematological problems (nutritional or otherwise). Neutrophils: after achieving neutrophil engraftment, there is a subsequent decrease in ANC such that the ANC falls to <0.5*10^9/L for at least 7 days regardless of growth factor support. Platelets: after achieving primary platelet engraftment, there was a subsequent decrease in platelet counts below 10*10^9/L for 7 days (defined by at least 2 consecutive platelet laboratory values obtained over at least 7 days) or required sustained platelet transfusion support. Analysis was performed on safety set for stage 2. Number of subjects analysed=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to 24 months post-transplant or until disease recurrence or progression whichever occurred first (up to a maximum duration of 2.5 years)

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	10	23
Units: percentage of subjects
number (not applicable)
Secondary neutrophil graft failure	0	0
Secondary platelet graft failure	0	4.3

No statistical analyses for this end point

Secondary: Stage 2: Median Time to Secondary Graft Failure

Top of page

End point title

Stage 2: Median Time to Secondary Graft Failure ^[16]

End point description

Median time to secondary graft failure was defined as the time interval from the date of successful engraftment to the date of documented secondary graft failure for those subjects who had achieved successful engraftment. Subjects without graft failure at the end of the follow-up period were to be censored at the last visit. Analysis was performed using Kaplan-Meier method. Analysis was performed on safety set for stage 2. Here, 99999 represents data not calculated as no subjects had event (secondary graft failure).

End point type

Secondary

End point timeframe

From date of engraftment till the graft failure (up to a maximum duration of 2.5 years)

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	15	30
Units: months
number (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Stage 2: Overall Survival at Month 3, 6, 12 and 24 Post- Transplant

Top of page

End point title

Stage 2: Overall Survival at Month 3, 6, 12 and 24 Post- Transplant ^[17]

End point description

Overall survival for subjects who received transplant(s) was defined as the time interval from the date of transplantation to the date of death. Subjects alive at the end of the follow-up period were to be censored at the last follow-up visit with known alive status. Kaplan-Meier method was used to estimate the confidence intervals (CIs), using a log transformation. Percentage of subjects with OS were estimated. Analysis was performed on safety set for stage 2. Number of subjects analysed=subjects evaluable for this endpoint. Here, 99999 represents data (95% CI) not calculated as very low number of subjects had event.

End point type

Secondary

End point timeframe

At 3, 6, 12 and 24 Months Post Transplant (up to a maximum duration of 2.5 years)

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	10	23
Units: percentage of subjects
number (confidence interval 95%)
Month 3	1 (-99999 to 99999)	0.957 (0.729 to 0.994)
Month 6	0.9 (0.473 to 0.985)	0.957 (0.729 to 0.994)
Month 12	0.9 (0.473 to 0.985)	0.957 (0.729 to 0.994)
Month 24	0.675 (0.291 to 0.882)	0.87 (0.648 to 0.956)

No statistical analyses for this end point

Secondary: Stage 2: Overall Survival Rate for Subjects at 3, 6, 12 and 24 Months Post Apheresis

Top of page

End point title

Stage 2: Overall Survival Rate for Subjects at 3, 6, 12 and 24 Months Post Apheresis ^[18]

End point description

Overall survival for all subjects was calculated as the time interval from the date of last apheresis to the date of death. Subjects alive at the end of the follow-up period were to be censored at the last follow-up visit with known alive status. Kaplan-Meier method was used to estimate the CIs, using a log transformation Percentage of subjects with OS were estimated. Analysis was performed on safety set for stage 2. Here, 99999 represents data (95% CI) not calculated as very low number of subjects had event.

End point type

Secondary

End point timeframe

At 3, 6, 12 and 24 Months Post Apheresis (up to a maximum duration of 2.5 years)

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.

End point values	Stage 2: Standard Mobilization Regimen - G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Number of subjects analysed	15	30
Units: percentage of subjects
number (confidence interval 95%)
Month 3	1 (-99999 to 99999)	1 (-99999 to 99999)
Month 6	1 (-99999 to 99999)	1 (-99999 to 99999)
Month 12	0.929 (0.591 to 0.99)	0.964 (0.772 to 0.995)
Month 24	0.766 (0.433 to 0.919)	0.893 (0.704 to 0.964)

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (up to post-transplant follow up visit of 2 years) regardless of seriousness or relationship to investigational product.

Adverse event reporting additional description

Reported AEs are TEAEs that is AEs that developed/worsened during the on treatment period (from the date of randomization until 30 days after the last dose of subject’s study mobilization regimen, or until the first dose of their next anticancer therapy or pre-transplant myeloablative therapy or 2-year follow-up period).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Stage 1: Plerixafor 160 mcg /kg: 2-<6 years

Reporting group description

Reporting group title

Stage 1: Plerixafor 240 mcg /kg: 2-<6 years

Reporting group description

Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 320 mcg /kg: 2-<6 years

Reporting group description

Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 160 mcg /kg: 6-<12 years

Reporting group description

Reporting group title

Stage 1: Plerixafor 240 mcg /kg: 6-<12 years

Reporting group description

Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 320 mcg /kg: 6-<12 years

Reporting group description

Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 160 mcg /kg: 12-<18 years

Reporting group description

Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 240 mcg/kg: 12-<18 years

Reporting group description

Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 1: Plerixafor 320 mcg/kg: 12-<18 years

Reporting group description

Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

Reporting group title

Stage 2: Standard Mobilization Regimen- G-CSF

Reporting group description

Reporting group title

Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF

Reporting group description

Serious adverse events	Stage 1: Plerixafor 160 mcg /kg: 2-<6 years	Stage 1: Plerixafor 240 mcg /kg: 2-<6 years	Stage 1: Plerixafor 320 mcg /kg: 2-<6 years	Stage 1: Plerixafor 160 mcg /kg: 6-<12 years	Stage 1: Plerixafor 240 mcg /kg: 6-<12 years	Stage 1: Plerixafor 320 mcg /kg: 6-<12 years	Stage 1: Plerixafor 160 mcg /kg: 12-<18 years	Stage 1: Plerixafor 240 mcg/kg: 12-<18 years	Stage 1: Plerixafor 320 mcg/kg: 12-<18 years	Stage 2: Standard Mobilization Regimen- G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	9 / 30 (30.00%)	4 / 15 (26.67%)
number of deaths (all causes)	0	0	0	1	0	1	0	1	1	3	3
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Blood Stem Cell Harvest Failure
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Bone Marrow Harvest
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Hydrocephalus
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Bone Marrow Failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile Neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	3 / 30 (10.00%)	2 / 15 (13.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 30 (6.67%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 30 (6.67%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal Inflammation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterobacter Bacteraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Stage 1: Plerixafor 160 mcg /kg: 2-<6 years	Stage 1: Plerixafor 240 mcg /kg: 2-<6 years	Stage 1: Plerixafor 320 mcg /kg: 2-<6 years	Stage 1: Plerixafor 160 mcg /kg: 6-<12 years	Stage 1: Plerixafor 240 mcg /kg: 6-<12 years	Stage 1: Plerixafor 320 mcg /kg: 6-<12 years	Stage 1: Plerixafor 160 mcg /kg: 12-<18 years	Stage 1: Plerixafor 240 mcg/kg: 12-<18 years	Stage 1: Plerixafor 320 mcg/kg: 12-<18 years	Stage 2: Standard Mobilization Regimen- G-CSF	Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
Total subjects affected by non serious adverse events
subjects affected / exposed	2 / 3 (66.67%)	1 / 3 (33.33%)	2 / 3 (66.67%)	3 / 3 (100.00%)	2 / 3 (66.67%)	2 / 3 (66.67%)	3 / 3 (100.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	20 / 30 (66.67%)	10 / 15 (66.67%)
Vascular disorders
Hyperaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Hypertension
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Hypotension
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
General disorders and administration site conditions
Catheter Site Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Chest Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Extravasation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Fatigue
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	3 / 15 (20.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	4
Injection Site Reaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 30 (6.67%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0
Malaise
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Mucosal Inflammation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Pyrexia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)
occurrences all number	1	0	1	0	0	0	1	0	0	1	1
Immune system disorders
Drug Hypersensitivity
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 30 (6.67%)	1 / 15 (6.67%)
occurrences all number	1	0	0	0	0	0	0	0	0	2	1
Increased Viscosity Of Upper Respiratory Secretion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Rhinorrhoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 30 (6.67%)	2 / 15 (13.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	2
Antithrombin Iii Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Aspartate Aminotransferase Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 30 (6.67%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	1
Blood Bicarbonate Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Echocardiogram Abnormal
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Platelet Count Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	6 / 30 (20.00%)	2 / 15 (13.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	6	2
Weight Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Injury, poisoning and procedural complications
Allergic Transfusion Reaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Back Injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Brain Contusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Infusion Related Reaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Procedural Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Thermal Burn
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Cardiac disorders
Tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 30 (6.67%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	3	2	0
Intracranial Venous Sinus Thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Seizure
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	9 / 30 (30.00%)	3 / 15 (20.00%)
occurrences all number	0	0	1	1	0	0	0	0	1	9	3
Febrile Neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Hypofibrinogenaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Leukopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1
Thrombocytopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	1
Ear and labyrinth disorders
Deafness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Eye disorders
Optic Atrophy
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Pupils Unequal
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Vision Blurred
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal Distension
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Abdominal Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 30 (10.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	3	0
Abdominal Pain Upper
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	1
Constipation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1
Dental Caries
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1
Diarrhoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 30 (10.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	3	0	0	4	1
Dyspepsia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Lip Dry
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Nausea
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 30 (6.67%)	3 / 15 (20.00%)
occurrences all number	0	0	0	1	1	0	0	1	1	3	4
Proctalgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Stomatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	1
Vomiting
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 30 (10.00%)	2 / 15 (13.33%)
occurrences all number	0	0	0	1	1	1	2	0	0	3	3
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Rash Papular
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Urticaria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Endocrine disorders
Cushingoid
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Back Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Pain In Extremity
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Conjunctivitis Viral
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Device Related Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Enterobacter Infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Escherichia Urinary Tract Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Febrile Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Otitis Media
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Rhinitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 30 (10.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	1	0	0	0	0	3	1
Staphylococcal Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Viral Upper Respiratory Tract Infection
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Hyperglycaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1
Hypoalbuminaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 30 (10.00%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	1
Hypocalcaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 30 (6.67%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	1
Hypokalaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	2 / 15 (13.33%)
occurrences all number	0	0	0	1	0	0	0	0	0	2	2
Hypomagnesaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Hyponatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Hypophosphataemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

04 Nov 2013

Following amendments were made: - Dose from phase I (stage 1 of the study) was incorporated for phase II use (stage 2). - Sub-grouping for stratification was changed based on information from stage 1 population recruited: Ewing’s and other STS; Lymphoma; Neuroblastoma; Other malignancies including brain tumours. - The age range for the study was modified to 1 to <18 years to allow potential inclusion of 1 to 2 year olds if feasible (no minimal number of 1-2 y old subjects required), as requested by the Paediatrics Development Committee of the EMA (PIP). - Modifications arising from discussions with the DMC and the Investigators following Stage 1 were incorporated, such as: • Timing of G CSF administration • Limited PK sampling timing • Selected Lab Value minimums for ANC and platelets. - Administrative details were updated from original Genzyme protocol to Sanofi standards and procedures (study management transferred to Sanofi).

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Stage 2: Percentage of Subjects Achieving At least a Doubling of Peripheral Blood CD34+ Count

Primary: Stage 2: Percentage of Subjects Achieving At least a Doubling of Peripheral Blood CD34+ Count

Secondary: Stage 2: Median Number of Days of Apheresis Required to Reach >=2 *10^6 CD34+ cells/kg

Secondary: Stage 2: Median Number of Days of Apheresis Required to Reach >=2 *10^6 CD34+ cells/kg

Secondary: Stage 2: Yield of CD34+ (*10^6 cells/kg ) Cells for Each Apheresis

Secondary: Stage 2: Yield of CD34+ (*10^6 cells/kg ) Cells for Each Apheresis

Secondary: Stage 2: Total CD34+ Cell Yield

Secondary: Stage 2: Total CD34+ Cell Yield

Secondary: Stage 2: Percentage of Subjects Proceeding to Autologous Transplant

Secondary: Stage 2: Percentage of Subjects Proceeding to Autologous Transplant

Secondary: Stage 2: Percentage of Subjects Successfully Engrafting

Secondary: Stage 2: Percentage of Subjects Successfully Engrafting

Secondary: Stage 2: Percentage of Subjects with Durable Engraftment

Secondary: Stage 2: Percentage of Subjects with Durable Engraftment

Secondary: Stage 1 and Stage 2: Overview of Safety

Secondary: Stage 1 and Stage 2: Overview of Safety

Secondary: Stage 2: Percentage of Subjects Who Had Hospitalization

Secondary: Stage 2: Percentage of Subjects Who Had Hospitalization

Secondary: Stage 2: Percentage of Subjects With Tumor Cell Mobilisation Positive in Peripheral Blood

Secondary: Stage 2: Percentage of Subjects With Tumor Cell Mobilisation Positive in Peripheral Blood

Secondary: Stage 2: Post-Transplant Relapse Rate

Secondary: Stage 2: Post-Transplant Relapse Rate

Secondary: Stage 2: Post-Apheresis Relapse Rate

Secondary: Stage 2: Post-Apheresis Relapse Rate

Secondary: Stage 2: Percentage of Subjects With Secondary Malignancies

Secondary: Stage 2: Percentage of Subjects With Secondary Malignancies

Secondary: Stage 2: Percentage of Subjects with Primary Graft Failure

Secondary: Stage 2: Percentage of Subjects with Primary Graft Failure

Secondary: Stage 2: Percentage of Subjects With Secondary Graft Failure

Secondary: Stage 2: Percentage of Subjects With Secondary Graft Failure

Secondary: Stage 2: Median Time to Secondary Graft Failure

Secondary: Stage 2: Median Time to Secondary Graft Failure

Secondary: Stage 2: Overall Survival at Month 3, 6, 12 and 24 Post- Transplant

Secondary: Stage 2: Overall Survival at Month 3, 6, 12 and 24 Post- Transplant

Secondary: Stage 2: Overall Survival Rate for Subjects at 3, 6, 12 and 24 Months Post Apheresis

Secondary: Stage 2: Overall Survival Rate for Subjects at 3, 6, 12 and 24 Months Post Apheresis

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information