Clinical Trials Register

Summary
EudraCT Number:	2010-023436-16
Sponsor's Protocol Code Number:	HOVON107
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Restarted
Date on which this record was first entered in the EudraCT database:	2013-06-13
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2010-023436-16

A.3

Full title of the trial

The feasibility and efficacy of subcutaneous Plerixafor for mobilization of peripheral blood stem cells in allogeneic HLA–identical sibling donors: a prospective phase II study.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

The feasibility and efficacy of subcutaneous Plerixafor for mobilization of peripheral blood stem cells in allogeneic HLA–identical sibling donors: a prospective phase II study.

A.3.2

Name or abbreviated title of the trial where available

HOVON 107 MOBILIZATION

A.4.1

Sponsor's protocol code number

HOVON107

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	HOVON Foundation
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	HOVON
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	Genzyme
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	HOVON
B.5.2	Functional name of contact point	Trialmanager
B.5.3	Address:
B.5.3.1	Street Address	Groene hilledijk 301
B.5.3.2	Town/ city	Rotterdam
B.5.3.3	Post code	3075 EA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+310107041560
B.5.5	Fax number	+310107041028
B.5.6	E-mail	hdc@erasmusmc.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	MOZOBIL
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme Europe B.V.,
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/04/227
D.3 Description of the IMP
D.3.1	Product name	plerixafor
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Plerixafor
D.3.9.1	CAS number	110078-46-1
D.3.9.2	Current sponsor code	AMD3100, Mozobil
D.3.9.3	Other descriptive name	PLERIXAFOR
D.3.9.4	EV Substance Code	SUB28849
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	hematopoietic stem cells
D.3.2	Product code	HPCs
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

stem cell mobilization

E.1.1.1

Medical condition in easily understood language

stem cell mobilization

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10053948
E.1.2	Term	Hematopoietic stem cell mobilization
E.1.2	System Organ Class	100000004865

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10024329
E.1.2	Term	Leukemia
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	PT
E.1.2	Classification code	10028533
E.1.2	Term	Myelodysplastic syndrome
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the feasibility of plerixafor 320 μg/kg subcutaneously to harvest a sufficient number of CD34+ peripheral blood stem cells/kg recipient body weight.
Feasibilty is defined as a minimum of 2.0x106/kg CD34+ cells in one or two phereses in at least 90% of the donors

E.2.2

Secondary objectives of the trial

Donors:
1. To determine the efficacy (nr of CD34+ cells / liter processed blood volume) of plerixafor.
2. To determine the time interval that is required to obtain 2.0 x 106 CD34+ cells/kg .
3. To determine the number of CD34+ cells in the peripheral blood at regular intervals after the administration of plerixafor.
4. To determine the number of CD34+ cells in the peripheral blood and the apheresis product at regular intervals during the stem cell apheresis.
5. To determine the phenotype of plerixafor mobilized CD34+ cells both in peripheral blood and collected stem cells.
6. To document adverse events grade 1-4 following mobilization by plerixafor.

Patients:
1. To document engraftment 30, 60 and 90 days after transplantation with an allograft harvested after mobilization with plerixafor 320 μg/kg subcutaneously.
2. To document hematopietic reconstitution.
3. To study chimerism in peripheral blood and T-cells 30, 60 and 90 days, and chimerism in bone marrow 90 days .

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Donors
• HLA identical sibling donor
• Age 18-60 years inclusive
• Hematologic parameters within normal limits
• Capable of undergoing leucapheresis: adequate venous access. Must be willing to undergo insertion of a central catheter should leucapheresis via peripheral vein be inadequate
• Willing and able to have bone marrow aspiration if there is mobilization failure
• Negative pregnancy test at study entry for women of childbearing potential
• Willing and able to use adequate contraception during the mobilization and collection period
• Written informed consent from donor

Patients
• Age 18-65 years inclusive
• In general, indication for allogeneic stem cell transplant will be determined by each participating center according to local criteria
• Patients with a cytopathologically confirmed diagnosis of:
- De novo Acute Myeloid Leukemia according to WHO classification in first complete remission (excluding acute promyelocytic leukemia)
• Therapy related AML/RAEB in first complete remission
• Myelodysplasia RA(RS)/RCMD with IPSS ≥ 1.5
- Myelodysplasia refractory anemia with excess of blasts (RAEB) with IPSS ≥ 1.5 in first complete remission
• Biphenotypic leukemia in first complete remission OR
- De novo B or T Lineage Acute Lymphatic Leukemia in first complete remission.
• Multiple myeloma, not included in other transplant study
• Hodgkin Lymphoma
• Non-Hodgkin lymphoma
• Chronic lymfocytic leukemia
• Chronic myeloid leukemia
• WHO performance score 0, 1 or 2
• Patients should have an HLA- identical sibling donor
• Life expectancy >3 months
• Negative pregnancy test at study entry for women of childbearing potential
• Willing and able to use adequate contraception
• Written informed consent from patient

E.4

Principal exclusion criteria

Donors
• Monozygotic twin
• Unstable hypertension requiring more than 1 medication.
• Positive serology for hepatitis C or HbsAg
• Treatment with other investigational drugs
• HIV positivity
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Pregnant or breastfeeding female subject

Patients
• Cardiac dysfunction
• Severe pulmonary dysfunction (CTCAE grade 3-4)
• Severe neurological or psychiatric disease
• Significant hepatic dysfunction
• Significant renal dysfunction
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)
• Patient known to be HIV-positive
• Pregnant or breast-feeding female patients
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Presence of other active non-hematological malignancy

E.5 End points

E.5.1

Primary end point(s)

Percentage of donors in each arm with a successful harvest (≥2.0x106 CD34+ cells /kg).

E.5.1.1

Timepoint(s) of evaluation of this end point

The stem cell collection will take place the following day starting 9 hours after the subcutaneous administration of plerixafor.
Collection itself is a standard procedure and will take 4-5 hours. In case less than 2.0x106 CD34+cells/kg recipient body weight are collected the procedure (mobilization and collection) can be repeated the following day.

E.5.2

Secondary end point(s)

For donors:
1.The absolute number of CD34+ cells collected per litre processed volume.
2.The time required to collect 2.0x106 CD34+ cells/kg, also in relation to the time of administration of plerixafor.
3.The number of CD34+ cells in the peripheral blood at regular intervals after the administration of plerixafor.
4.The number of CD34+ cells in the peripheral blood as well as in the apheresis product at regular intervals during the stem cell apheresis.
5.The phenotype of CD34+ cells and hematopoietic progenitor cells including its subpopulations, dendritic cells as well as regulatory T-cells in peripheral blood and in the graft.
6.The incidence and CTCAE grade (1-4) of adverse events.
For patients:
1.Incidence of engraftment at days 30, 60 and 90 after transplantation with plerixafor mobilized HPCs.
2.Time to hematopoietic reconstitution.
3.Hematopoietic chimerism in blood, CD3 isolated cells at days 30, 60, 90 after transplantation and in bone marrow at day 90 after transplantation.
4.Incidence and grade of GVHD.

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

last subject last visit

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Donor follow-up will take place after 6 weeks, 6 months, 1 year and 2 years
Patient follow up will take place after 3, 6, 12, 18, 24 months

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-11-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-27

P. End of Trial
P.	End of Trial Status	Restarted

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