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Clinical Trial Results:
High-dose chemotherapy and autologous stem cell transplant or consolidating conventional chemotherapy in primary CNS lymphoma - randomized phase III trial

Summary
EudraCT number	2012-000620-17
Trial protocol	DE DK NO IT
Global end of trial date	25 Feb 2022

Results information
Results version number	v2(current)
This version publication date	28 Mar 2024
First version publication date	22 Feb 2024
Other versions	v1
Version creation reason

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

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Trial information

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Sponsor protocol code

DRKS00005503

ISRCTN number

US NCT number

NCT02531841

WHO universal trial number (UTN)

Other trial identifiers

DRKS: 00005503

Sponsor organisation name

Klinikum Der Landeshauptstadt Stuttgart gKAöR

Sponsor organisation address

Kriegsbergstrasse 60, Stuttgart, Germany, 70174

Public contact

PD Dr. med. Elisabeth Schorb, Medical Center - University of Freiburg, Germany, +49 761 270 35361, elisabeth.schorb@uniklinik-freiburg.de

Scientific contact

PD Dr. med. Elisabeth Schorb, Medical Center - University of Freiburg, Germany, +49 761 270 35361, elisabeth.schorb@uniklinik-freiburg.de

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

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?

Analysis stage

Final

Date of interim/final analysis

18 Sep 2023

Is this the analysis of the primary completion data?

Yes

Primary completion date

09 Feb 2022

Global end of trial reached?

Yes

Global end of trial date

25 Feb 2022

Was the trial ended prematurely?

Main objective of the trial

To demonstrate the efficacy measured as progression-free survival (PFS) of intensive chemotherapy followed by autologous stem-cell transplantation compared to conventional chemotherapy

Protection of trial subjects

Interim analyses regarding safety issues were performed regularly in order to inform the Data Monitoring Committee (DMC). The underlying principles for the DMC are the patients' ethical and safety aspects. It is the task of the DMC to examine whether the study’s conduct is still ethically justifiable, whether security of the patients is ensured and whether the study’s conduct is acceptable. Data on the patient's vital signs were taken at screening and all subsequent visits. The patient was free to withdraw from the study for any reason and at any time without giving reason for doing so and without penalty or prejudice.

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Jul 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Norway: 4

Country: Number of subjects enrolled

Denmark: 11

Country: Number of subjects enrolled

Germany: 284

Country: Number of subjects enrolled

Italy: 46

Country: Number of subjects enrolled

Switzerland: 1

Worldwide total number of subjects

346

EEA total number of subjects

345

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)

262

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Number of subjects started

346

Number of subjects completed

346

Period 1 title

Induction treatment

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Single arm treatment period

Induction treatment

Arm description

4 cycles (every 3 weeks), stem-cell harvest after 2nd cycle: - Rituximab 375 mg/m²/d i.v. (days 0, 5) - MTX 3.5 g/m² i.v. (day 1) - Ara-C 2 x 2 g/m²/d i.v. (days 2-3) - Thiotepa 30 mg/m2 i.v. (day 4)

Arm type

Induction treatment

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

MabThera®

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Concentrate for solution for infusion

Dosage and administration details

Strength: 10 mg/mL (referred to concentrate) Dose: 3000 mg/m2 (total), for induction treatment and consolidation treatment For induction treatment: 375 mg/m²/d i.v. (day 0, 5)

Investigational medicinal product name

Thiotepa

Investigational medicinal product code

Other name

TEPADINA® 100 mg

Pharmaceutical forms

Powder for concentrate for solution for infusion

Routes of administration

Solution for infusion

Dosage and administration details

Strength: 10 mg/mL (refers to concentrate) Dose: 30 mg/kg (total), For induction treatment: 30 mg/m2 i.v. (day 4)

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

ARA-cell® 4000 mg Infusionslösung

Pharmaceutical forms

Solution for infusion

Routes of administration

Solution for infusion

Dosage and administration details

Strength: 50 mg/mL Dose: 32 g/m2 (total) For induction treatment: 2 x 2 g/m²/d i.v. (days 2-3)

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Methotrexat HC 1000 mg Lösung Medac

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Concentrate for solution for infusion

Dosage and administration details

Strength: 100 mg/mL MTX (referred to concentrate) Dose: 14 g/m2 (total), for induction treatment For induction treatment: 3.5 g/m² i.v. (day 1)

Number of subjects in period 1	Induction treatment
Started	346
Completed	230
Not completed	116
incl. insufficient bone marrow recovery	15
Toxicity, AE/SAE	56
Wish of patient	5
Protocol deviation	40

Period 2 title

Consolidation treatment

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

R-DeVIC

Arm description

2 cycles of R-DeVIC (every 3 weeks): - Rituximab 375 mg/m²/d i.v. (d 0) - Dexamethasone 40 mg/d i.v. (d 1-3) - Etoposide 100 mg/m²/d i.v. (d 1-3) - Ifosfamide 1500 mg/m²/d i.v. (d 1-3) - Carboplatin 300 mg/m² i.v. (d 1)

Arm type

Active comparator

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

ARA-cell® 4000 mg Infusionslösung

Pharmaceutical forms

Solution for infusion

Routes of administration

Solution for infusion

Dosage and administration details

Strength: 50 mg/mL Dose: 32 g/m2 (total), for induction treatment

Investigational medicinal product name

Methotrexate

Investigational medicinal product code

Other name

Methotrexat HC 1000 mg Lösung Medac

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Concentrate for solution for infusion

Dosage and administration details

Strength: 100 mg/mL MTX (referred to concentrate) Dose: 14 g/m2 (total), for induction treatment

Investigational medicinal product name

Thiotepa

Investigational medicinal product code

Other name

TEPADINA® 100 mg

Pharmaceutical forms

Powder for concentrate for solution for infusion

Routes of administration

Solution for infusion

Dosage and administration details

Strength: 10 mg/mL (refers to concentrate) Dose: 30 mg/kg (total), for induction treatment, 20 mg/kg (total), for high-dose consolidation

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

MabThera®

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Concentrate for solution for infusion

Dosage and administration details

Strength: 10 mg/mL (referred to concentrate) Dose: 3000 mg/m2 (total), for induction treatment and consolidation treatment For consolidation treatment: 375 mg/m² i.v. (day 0)

Investigational medicinal product name

Busulfan

Investigational medicinal product code

Other name

Busilvex®

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Concentrate for solution for infusion

Dosage and administration details

Strength: 6 mg/mL (refers to concentrate) Dose: 6.4 mg/ml (total)

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Fortecortin® Inject 40 mg

Pharmaceutical forms

Solution for injection

Routes of administration

Solution for injection

Dosage and administration details

Strength: 8,744 mg/ml Dexamethason-21-dihydrogen phosphate disodium (= 8 mg/ml dexamethasone) Dose: 240 mg (total), for consolidation Arm A

Investigational medicinal product name

Etoposide/VP-16

Investigational medicinal product code

Other name

ETOPOPHOS® 1000 mg

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Solution for infusion

Dosage and administration details

Strength: 11,4 mg/mL Etoposide phosphate (= 10 mg/mL Etoposide, referred to concentrate) Dose: 600 mg/m2 (total), for consolidation Arm A

Investigational medicinal product name

Ifosfamide

Investigational medicinal product code

Other name

IFO-cell® 5 g

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Concentrate for solution for infusion

Dosage and administration details

Strength: 200 mg/mL Dose: 9000 mg/m2 (total), for consolidation Arm A

Investigational medicinal product name

Carmustine/BCNU

Investigational medicinal product code

Other name

CARMUBRIS®

Pharmaceutical forms

Powder and solvent for solution for infusion

Routes of administration

Solution for infusion

Dosage and administration details

Strength: 3.3 mg/mL (refers to concentrate) Dose: 400 mg/m2 (total), for consolidation in experimental intervention

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

CARBO-cell® 10 mg/mL Infusionslösung

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Concentrate for solution for infusion

Dosage and administration details

Strength: 10 mg/mL Dose: 600 mg/m2 (total), for consolidation Arm A

HDT-ASCT

Arm description

High-dose chemotherapy (HDT): - BCNU* 400 mg/m² i.v. (d -6) - Thiotepa 2 x 5 mg/kg/d i.v. (d -5-(-4)) - ASCT (d 0) * if not available at study site, Busulfan could have been administered: Busulfan 3.2 mg/kg/d i.v. (d -8-(-7))

Arm type

Experimental

Investigational medicinal product name

Thiotepa

Investigational medicinal product code

Other name

TEPADINA® 100 mg

Pharmaceutical forms

Powder for concentrate for solution for infusion

Routes of administration

Solution for infusion

Dosage and administration details

Strength: 10 mg/mL (refers to concentrate) Dose: 30 mg/kg (total), For consolidation treatment: 2 x 5 mg/kg/d i.v. (d -5-(-4))

Investigational medicinal product name

Carmustine/BCNU

Investigational medicinal product code

Other name

CARMUBRIS®

Pharmaceutical forms

Powder and solvent for solution for infusion

Routes of administration

Solution for infusion

Dosage and administration details

Strength: 3.3 mg/mL (refers to concentrate) Dose: 400 mg/m2 (total). For consolidation treatment: BCNU 400 mg/m² i.v. (d -6). If not available at study site, Busulfan could have been administered: Busulfan 3.2 mg/kg/d i.v. (d -8-(-7))

Number of subjects in period 2	R-DeVIC	HDT-ASCT
Started	115	115
Completed	115	114
Not completed	0	1
Major I/E violation	-	1

Baseline characteristics

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Reporting group title

Induction treatment

Reporting group description

Reporting group values	Induction treatment	Total
Number of subjects	346	346
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	262	262
From 65-84 years	84	84
85 years and over	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	57.8 ( 9.5 )	-
Gender categorical
Units: Subjects
Female	150	150
Male	196	196

End points

Top of page

Reporting group title

Induction treatment

Reporting group description

Reporting group title

R-DeVIC

Reporting group description

Reporting group title

HDT-ASCT

Reporting group description

Primary: Progression-free survival (FAS)

Top of page

End point title

Progression-free survival (FAS)

End point description

End point type

Primary

End point timeframe

Time from randomization until disease progression), disease relapse after achieving complete response (CR), or death from any cause.

End point values	R-DeVIC	HDT-ASCT
Number of subjects analysed	115	114
Units: Rate
number (confidence interval 95%)
6 months	0.83 (0.74 to 0.88)	0.83 (0.75 to 0.89)
12 months	0.71 (0.62 to 0.78)	0.83 (0.74 to 0.88)
24 months	0.61 (0.51 to 0.69)	0.79 (0.70 to 0.85)
36 months	0.51 (0.41 to 0.60)	0.78 (0.69 to 0.85)
48 months	0.50 (0.40 to 0.59)	0.77 (0.67 to 0.83)
60 months	0.46 (0.35 to 0.56)	0.74 (0.62 to 0.82)

Cox regression analysis

Statistical analysis description

The primary endpoint PFS was analyzed with a Cox proportional hazards model, containing the randomized treatment as hypothesis variable and the stratification variable response status as a covariate.

Comparison groups

R-DeVIC v HDT-ASCT

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

equivalence

P-value

= 0.0003

Method

Regression, Cox

Parameter type

Cox proportional hazard

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.27

upper limit

0.68

Secondary: Overall survival (FAS)

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End point title

Overall survival (FAS)

End point description

End point type

Secondary

End point timeframe

Time from randomization until death from any cause.

End point values	R-DeVIC	HDT-ASCT
Number of subjects analysed	115	114
Units: Rate
number (confidence interval 95%)
6 months	0.96 (0.90 to 0.98)	0.93 (0.86 to 0.96)
12 months	0.89 (0.81 to 0.93)	0.91 (0.84 to 0.95)
24 months	0.80 (0.72 to 0.87)	0.87 (0.79 to 0.92)
36 months	0.71 (0.61 to 0.78)	0.86 (0.78 to 0.91)
48 months	0.68 (0.58 to 0.76)	0.84 (0.76 to 0.90)
60 months	0.63 (0.52 to 0.73)	0.84 (0.76 to 0.90)

Hazard Ratio

Comparison groups

R-DeVIC v HDT-ASCT

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

0.81

Secondary: Relapse rate

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End point title

Relapse rate

End point description

End point type

Secondary

End point timeframe

Time from randomization

End point values	R-DeVIC	HDT-ASCT
Number of subjects analysed	115	114
Units: Rate
number (confidence interval 95%)
6 months	0.1667 (0.1048 to 0.2409)	0.1316 (0.0772 to 0.2008)
12 months	0.2725 (0.1940 to 0.3567)	0.1404 (0.0839 to 0.2109)
24 months	0.3736 (0.2842 to 0.4629)	0.1770 (0.1129 to 0.2530)
36 months	0.4494 (0.3519 to 0.5419)	0.1864 (0.1204 to 0.2636)
48 months	0.4636 (0.3640 to 0.5572)	0.1994 (0.1300 to 0.2796)
60 months	0.4820 (0.3784 to 0.5782)	0.2300 (0.1433 to 0.3289)

No statistical analyses for this end point

Secondary: Non Relapse Mortality (FAS)

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End point title

Non Relapse Mortality (FAS)

End point description

End point type

Secondary

End point timeframe

Time from randomization to death without prior relapse / disease progression

End point values	R-DeVIC	HDT-ASCT
Number of subjects analysed	115	114
Units: Rate
number (confidence interval 95%)
6 months	0.0088 (0.0008 to 0.0437)	0.0351 (0.0114 to 0.0813)
12 months	0.0175 (0.0034 to 0.0565)	0.0351 (0.0114 to 0.0813)
24 months	0.0175 (0.0034 to 0.0565)	0.0351 (0.0114 to 0.0813)
36 months	0.0386 (0.0124 to 0.0896)	0.0351 (0.0114 to 0.0813)
48 months	0.0386 (0.0124 to 0.0896)	0.0351 (0.0114 to 0.0813)
60 months	0.0626 (0.0200 to 0.1404)	0.0351 (0.0114 to 0.0813)

No statistical analyses for this end point

Secondary: Quality of life EORTC QLQ-C30: 1 year follow-up

Top of page

End point title

Quality of life EORTC QLQ-C30: 1 year follow-up

End point description

End point type

Secondary

End point timeframe

1 year follow up

End point values	R-DeVIC	HDT-ASCT
Number of subjects analysed	115	114
Units: Points
arithmetic mean (standard deviation)
1 year follow-up	63.6 ( 20.1 )	64.9 ( 20.8 )

No statistical analyses for this end point

Secondary: Quality of life EORTC QLQ-C30: EOT change from screening

Top of page

End point title

Quality of life EORTC QLQ-C30: EOT change from screening

End point description

Only patients with paired values before and after therapy were considered

End point type

Secondary

End point timeframe

From screening to end of treatment

End point values	R-DeVIC	HDT-ASCT
Number of subjects analysed	115	114
Units: Points
arithmetic mean (standard deviation)
Change from screening to end of treatment	6.9 ( 31.4 )	8.3 ( 29.7 )

No statistical analyses for this end point

Secondary: Quality of life EORTC QLQ-C30: 1 year follow-up: change from screening

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End point title

Quality of life EORTC QLQ-C30: 1 year follow-up: change from screening

End point description

Only patients with paired values before and after therapy were considered.

End point type

Secondary

End point timeframe

From screening to 1 year follow up

End point values	R-DeVIC	HDT-ASCT
Number of subjects analysed	115	114
Units: Points
arithmetic mean (standard deviation)
1 year follow-up: change from screening	11.0 ( 30.1 )	14.8 ( 27.5 )

No statistical analyses for this end point

Secondary: Quality of life EORTC QLQ-C30: Screening

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End point title

Quality of life EORTC QLQ-C30: Screening

End point description

End point type

Secondary

End point timeframe

at screening

End point values	R-DeVIC	HDT-ASCT
Number of subjects analysed	115	114
Units: Points
arithmetic mean (standard deviation)
Screening	49.8 ( 26.1 )	47.1 ( 27.2 )

No statistical analyses for this end point

Secondary: Quality of life EORTC QLQ-C30: Response assessment II

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End point title

Quality of life EORTC QLQ-C30: Response assessment II

End point description

End point type

Secondary

End point timeframe

Response assessment II

End point values	R-DeVIC	HDT-ASCT
Number of subjects analysed	115	114
Units: Points
arithmetic mean (standard deviation)
Response assessment II	55.0 ( 21.6 )	57.5 ( 19.5 )

No statistical analyses for this end point

Secondary: Quality of life EORTC QLQ-C30: EOT

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End point title

Quality of life EORTC QLQ-C30: EOT

End point description

End point type

Secondary

End point timeframe

End of treatment

End point values	R-DeVIC	HDT-ASCT
Number of subjects analysed	115	114
Units: Points
arithmetic mean (standard deviation)
End of treatment	57.7 ( 20.9 )	53.1 ( 51.0 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Complete study

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Arm A (R-DeVic)

Reporting group description

Reporting group title

Induction therapy

Reporting group description

Reporting group title

Arm B (HDT-ASCT)

Reporting group description

Serious adverse events	Arm A (R-DeVic)	Induction therapy	Arm B (HDT-ASCT)
Total subjects affected by serious adverse events
subjects affected / exposed	25 / 108 (23.15%)	200 / 346 (57.80%)	29 / 111 (26.13%)
number of deaths (all causes)	36	63	17
number of deaths resulting from adverse events	2	18	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
subjects affected / exposed	2 / 108 (1.85%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	2 / 2	0 / 0	0 / 0
Myelodysplastic syndrome
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Jugular vein thrombosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mucosal inflammation
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 108 (0.00%)	11 / 346 (3.18%)	2 / 111 (1.80%)
occurrences causally related to treatment / all	0 / 0	6 / 11	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Acute respiratory distress syndrome
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
Epistaxis
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemothorax
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypercapnia
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lung infiltration
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Respiratory arrest
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Psychiatric disorders
Acute psychosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Confusional state
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Self-injurious ideation
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	1 / 108 (0.93%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chemotherapeutic drug level increased
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
C-reactive protein increased
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eastern Cooperative Oncology Group performance status worsened
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemoglobin decreased
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	2 / 108 (1.85%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	2 / 2	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Brain herniation
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemolytic transfusion reaction
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seroma
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transplant failure
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound dehiscence
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Brain oedema
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Cerebral haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebellar syndrome
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	1 / 108 (0.93%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dysarthria
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hydrocephalus
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoaesthesia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
IIIrd nerve paralysis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meningism
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neurotoxicity
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 108 (0.93%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subdural hygroma
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 108 (2.78%)	8 / 346 (2.31%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	3 / 3	7 / 8	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bicytopenia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytopenia
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile bone marrow aplasia
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	3 / 108 (2.78%)	45 / 346 (13.01%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	3 / 3	55 / 57	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 108 (0.00%)	5 / 346 (1.45%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	4 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	2 / 108 (1.85%)	11 / 346 (3.18%)	3 / 111 (2.70%)
occurrences causally related to treatment / all	2 / 2	17 / 17	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	4 / 108 (3.70%)	13 / 346 (3.76%)	2 / 111 (1.80%)
occurrences causally related to treatment / all	4 / 4	13 / 14	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Colitis ischaemic
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticular perforation
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mechanical ileus
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Proctitis ulcerative
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	3 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Vomiting
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatotoxicity
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gallbladder rupture
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Hyperhidrosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 108 (0.00%)	12 / 346 (3.47%)	4 / 111 (3.60%)
occurrences causally related to treatment / all	0 / 0	11 / 12	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 108 (0.00%)	4 / 346 (1.16%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	3 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal tubular disorder
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
Diabetes insipidus
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Bone pain
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Muscle spasms
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abscess jaw
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Brain abscess
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 108 (0.93%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacterial sepsis
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atypical mycobacterial infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Candida sepsis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Cerebral candidiasis
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related sepsis
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 108 (0.93%)	5 / 346 (1.45%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection reactivation
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	0 / 108 (0.00%)	4 / 346 (1.16%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia bacteraemia
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocarditis staphylococcal
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Empyema
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
H1N1 influenza
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Gastroenteritis Escherichia coli
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Herpes zoster infection neurological
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	0 / 108 (0.00%)	7 / 346 (2.02%)	2 / 111 (1.80%)
occurrences causally related to treatment / all	0 / 0	5 / 8	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Klebsiella infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mucormycosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Medical device site infection
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Necrotising soft tissue infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutropenic infection
subjects affected / exposed	1 / 108 (0.93%)	8 / 346 (2.31%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	7 / 8	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutropenic sepsis
subjects affected / exposed	0 / 108 (0.00%)	5 / 346 (1.45%)	3 / 111 (2.70%)
occurrences causally related to treatment / all	0 / 0	5 / 5	3 / 3
deaths causally related to treatment / all	0 / 0	1 / 1	1 / 1
Osteomyelitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteomyelitis bacterial
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Parainfluenzae virus infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	2 / 108 (1.85%)	24 / 346 (6.94%)	4 / 111 (3.60%)
occurrences causally related to treatment / all	1 / 2	20 / 26	3 / 4
deaths causally related to treatment / all	0 / 0	4 / 4	2 / 2
Pneumonia necrotising
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia cytomegaloviral
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia escherichia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia fungal
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
Pneumonia influenzal
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia klebsiella
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural infection
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pseudomembranous colitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rectal abscess
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
Puncture site abscess
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pseudomonal sepsis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
Respiratory tract infection viral
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal sepsis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 108 (0.00%)	18 / 346 (5.20%)	2 / 111 (1.80%)
occurrences causally related to treatment / all	0 / 0	12 / 19	2 / 2
deaths causally related to treatment / all	0 / 0	3 / 3	1 / 1
Septic shock
subjects affected / exposed	0 / 108 (0.00%)	8 / 346 (2.31%)	3 / 111 (2.70%)
occurrences causally related to treatment / all	0 / 0	7 / 9	3 / 3
deaths causally related to treatment / all	0 / 0	3 / 3	0 / 0
Skin infection
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	3 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound abscess
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gout
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypernatraemia
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	2 / 111 (1.80%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Arm A (R-DeVic)	Induction therapy	Arm B (HDT-ASCT)
Total subjects affected by non serious adverse events
subjects affected / exposed	108 / 108 (100.00%)	344 / 346 (99.42%)	111 / 111 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasma cell myeloma
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences all number	1	0	0
Prostate cancer
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Embolism
subjects affected / exposed	3 / 108 (2.78%)	31 / 346 (8.96%)	2 / 111 (1.80%)
occurrences all number	3	31	2
Flushing
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	1 / 111 (0.90%)
occurrences all number	0	1	1
Haematoma
subjects affected / exposed	0 / 108 (0.00%)	5 / 346 (1.45%)	0 / 111 (0.00%)
occurrences all number	0	5	0
Hypertension
subjects affected / exposed	17 / 108 (15.74%)	94 / 346 (27.17%)	28 / 111 (25.23%)
occurrences all number	17	94	28
Hypotension
subjects affected / exposed	7 / 108 (6.48%)	48 / 346 (13.87%)	15 / 111 (13.51%)
occurrences all number	7	50	15
Jugular vein thrombosis
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Phlebitis
subjects affected / exposed	0 / 108 (0.00%)	10 / 346 (2.89%)	2 / 111 (1.80%)
occurrences all number	0	10	2
Subclavian vein thrombosis
subjects affected / exposed	1 / 108 (0.93%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	1	1	0
Thrombophlebitis superficial
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Thrombosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Superficial vein thrombosis
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences all number	1	0	0
Surgical and medical procedures
Lung lobectomy
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Tooth extraction
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Chills
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Chest pain
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Device related thrombosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Face oedema
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Fatigue
subjects affected / exposed	25 / 108 (23.15%)	110 / 346 (31.79%)	37 / 111 (33.33%)
occurrences all number	25	112	37
Gait disturbance
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Impaired healing
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Influenza like illness
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Infusion site extravasation
subjects affected / exposed	2 / 108 (1.85%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	2	1	0
Injection site haematoma
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Injection site haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Localised oedema
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Mucosal inflammation
subjects affected / exposed	1 / 108 (0.93%)	1 / 346 (0.29%)	1 / 111 (0.90%)
occurrences all number	1	1	1
Multiple organ dysfunction syndrome
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Oedema
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Oedema peripheral
subjects affected / exposed	19 / 108 (17.59%)	106 / 346 (30.64%)	21 / 111 (18.92%)
occurrences all number	19	108	21
Pain
subjects affected / exposed	14 / 108 (12.96%)	119 / 346 (34.39%)	25 / 111 (22.52%)
occurrences all number	14	120	25
Pyrexia
subjects affected / exposed	10 / 108 (9.26%)	164 / 346 (47.40%)	49 / 111 (44.14%)
occurrences all number	10	169	49
Swelling face
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 108 (0.93%)	32 / 346 (9.25%)	11 / 111 (9.91%)
occurrences all number	1	32	11
Reproductive system and breast disorders
Penis disorder
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Respiratory, thoracic and mediastinal disorders
Aspiration
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	1 / 111 (0.90%)
occurrences all number	0	1	1
Asthma
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Atelectasis
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Cough
subjects affected / exposed	0 / 108 (0.00%)	7 / 346 (2.02%)	3 / 111 (2.70%)
occurrences all number	0	7	3
Epistaxis
subjects affected / exposed	6 / 108 (5.56%)	67 / 346 (19.36%)	10 / 111 (9.01%)
occurrences all number	6	68	10
Dyspnoea
subjects affected / exposed	4 / 108 (3.70%)	55 / 346 (15.90%)	8 / 111 (7.21%)
occurrences all number	4	55	8
Hiccups
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	2 / 111 (1.80%)
occurrences all number	0	2	2
Hypoxia
subjects affected / exposed	0 / 108 (0.00%)	11 / 346 (3.18%)	1 / 111 (0.90%)
occurrences all number	0	11	1
Lung diffusion disorder
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Oropharyngeal pain
subjects affected / exposed	0 / 108 (0.00%)	4 / 346 (1.16%)	2 / 111 (1.80%)
occurrences all number	0	4	2
Pleural effusion
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Pleuritic pain
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	2 / 111 (1.80%)
occurrences all number	0	2	2
Pneumothorax
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Pulmonary haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Respiratory failure
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	1 / 111 (0.90%)
occurrences all number	0	5	1
Anxiety
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	4	0
Confusional state
subjects affected / exposed	9 / 108 (8.33%)	83 / 346 (23.99%)	17 / 111 (15.32%)
occurrences all number	9	83	17
Depressed mood
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Depression
subjects affected / exposed	13 / 108 (12.04%)	45 / 346 (13.01%)	10 / 111 (9.01%)
occurrences all number	13	45	10
Hallucination
subjects affected / exposed	1 / 108 (0.93%)	11 / 346 (3.18%)	6 / 111 (5.41%)
occurrences all number	1	11	6
Insomnia
subjects affected / exposed	7 / 108 (6.48%)	31 / 346 (8.96%)	6 / 111 (5.41%)
occurrences all number	8	31	6
Mania
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Panic attack
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Suicidal ideation
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	47 / 108 (43.52%)	280 / 346 (80.92%)	50 / 111 (45.05%)
occurrences all number	47	281	50
Aspartate aminotransferase increased
subjects affected / exposed	26 / 108 (24.07%)	230 / 346 (66.47%)	48 / 111 (43.24%)
occurrences all number	26	232	48
Blood alkaline phosphatase abnormal
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Blood bilirubin increased
subjects affected / exposed	8 / 108 (7.41%)	119 / 346 (34.39%)	18 / 111 (16.22%)
occurrences all number	8	119	18
Blood creatinine increased
subjects affected / exposed	21 / 108 (19.44%)	134 / 346 (38.73%)	24 / 111 (21.62%)
occurrences all number	21	137	24
Blood culture positive
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
C-reactive protein increased
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	4	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Electrocardiogram T wave inversion
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Forced expiratory volume decreased
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	2 / 111 (1.80%)
occurrences all number	0	3	2
Gamma-glutamyltransferase increased
subjects affected / exposed	51 / 108 (47.22%)	230 / 346 (66.47%)	71 / 111 (63.96%)
occurrences all number	51	232	71
Platelet count decreased
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Weight increased
subjects affected / exposed	2 / 108 (1.85%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	2	2	0
Weight decreased
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 108 (0.93%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	1	1	0
Fall
subjects affected / exposed	0 / 108 (0.00%)	12 / 346 (3.47%)	0 / 111 (0.00%)
occurrences all number	0	13	0
Infusion related reaction
subjects affected / exposed	1 / 108 (0.93%)	16 / 346 (4.62%)	12 / 111 (10.81%)
occurrences all number	1	16	12
Procedural pneumothorax
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Transfusion reaction
subjects affected / exposed	1 / 108 (0.93%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	1	1	0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Bradycardia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Atrial fibrillation
subjects affected / exposed	2 / 108 (1.85%)	12 / 346 (3.47%)	5 / 111 (4.50%)
occurrences all number	2	13	6
Palpitations
subjects affected / exposed	1 / 108 (0.93%)	9 / 346 (2.60%)	1 / 111 (0.90%)
occurrences all number	1	9	1
Sinus bradycardia
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	1 / 111 (0.90%)
occurrences all number	0	2	2
Sinus node dysfunction
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Sinus tachycardia
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	2 / 111 (1.80%)
occurrences all number	0	0	2
Tachycardia
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	1 / 111 (0.90%)
occurrences all number	0	2	1
Ventricular arrhythmia
subjects affected / exposed	0 / 108 (0.00%)	7 / 346 (2.02%)	2 / 111 (1.80%)
occurrences all number	0	7	2
Nervous system disorders
Balance disorder
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Cognitive disorder
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Dysgeusia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Dizziness
subjects affected / exposed	0 / 108 (0.00%)	11 / 346 (3.18%)	3 / 111 (2.70%)
occurrences all number	0	13	3
Dizziness postural
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Dysaesthesia
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Dysarthria
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Encephalopathy
subjects affected / exposed	2 / 108 (1.85%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences all number	2	0	0
Headache
subjects affected / exposed	14 / 108 (12.96%)	100 / 346 (28.90%)	14 / 111 (12.61%)
occurrences all number	14	100	14
Hemiplegia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Horner's syndrome
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences all number	1	0	0
Lethargy
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Leukoencephalopathy
subjects affected / exposed	1 / 108 (0.93%)	3 / 346 (0.87%)	2 / 111 (1.80%)
occurrences all number	1	3	2
Loss of consciousness
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Memory impairment
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Motor dysfunction
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Orthostatic intolerance
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Paraesthesia
subjects affected / exposed	6 / 108 (5.56%)	26 / 346 (7.51%)	3 / 111 (2.70%)
occurrences all number	6	26	3
Parkinsonism
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Partial seizures
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Peripheral motor neuropathy
subjects affected / exposed	3 / 108 (2.78%)	15 / 346 (4.34%)	1 / 111 (0.90%)
occurrences all number	3	15	1
Peripheral sensory neuropathy
subjects affected / exposed	7 / 108 (6.48%)	17 / 346 (4.91%)	1 / 111 (0.90%)
occurrences all number	7	17	1
Quadriparesis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Seizure
subjects affected / exposed	1 / 108 (0.93%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	1	3	0
Somnolence
subjects affected / exposed	5 / 108 (4.63%)	19 / 346 (5.49%)	5 / 111 (4.50%)
occurrences all number	5	19	5
Syncope
subjects affected / exposed	3 / 108 (2.78%)	17 / 346 (4.91%)	3 / 111 (2.70%)
occurrences all number	4	17	3
Tremor
subjects affected / exposed	1 / 108 (0.93%)	5 / 346 (1.45%)	1 / 111 (0.90%)
occurrences all number	1	5	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	102 / 108 (94.44%)	330 / 346 (95.38%)	103 / 111 (92.79%)
occurrences all number	102	336	103
Febrile neutropenia
subjects affected / exposed	14 / 108 (12.96%)	176 / 346 (50.87%)	67 / 111 (60.36%)
occurrences all number	14	182	67
Haemolysis
subjects affected / exposed	3 / 108 (2.78%)	6 / 346 (1.73%)	3 / 111 (2.70%)
occurrences all number	3	6	3
Leukopenia
subjects affected / exposed	89 / 108 (82.41%)	313 / 346 (90.46%)	101 / 111 (90.99%)
occurrences all number	89	313	101
Lymphadenopathy
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Neutropenia
subjects affected / exposed	74 / 108 (68.52%)	260 / 346 (75.14%)	85 / 111 (76.58%)
occurrences all number	74	261	85
Lymphopenia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	1 / 111 (0.90%)
occurrences all number	0	1	1
Thrombocytopenia
subjects affected / exposed	101 / 108 (93.52%)	330 / 346 (95.38%)	108 / 111 (97.30%)
occurrences all number	102	334	109
Thrombocytosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Hypoacusis
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Tinnitus
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Vertigo
subjects affected / exposed	0 / 108 (0.00%)	5 / 346 (1.45%)	0 / 111 (0.00%)
occurrences all number	0	5	0
Eye disorders
Conjunctival haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Diplopia
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences all number	1	0	0
Dry eye
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Eye haematoma
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Lacrimation increased
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Ocular hyperaemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Retinal haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Swelling of eyelid
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Vision blurred
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	1 / 111 (0.90%)
occurrences all number	0	3	1
Visual acuity reduced
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Visual field defect
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Visual impairment
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Vitreous haemorrhage
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences all number	1	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	6 / 108 (5.56%)	56 / 346 (16.18%)	23 / 111 (20.72%)
occurrences all number	6	56	23
Ascites
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	1 / 111 (0.90%)
occurrences all number	0	3	1
Aphthous ulcer
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Anal ulcer
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Anal fissure
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Colitis
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Constipation
subjects affected / exposed	12 / 108 (11.11%)	74 / 346 (21.39%)	9 / 111 (8.11%)
occurrences all number	13	74	9
Diarrhoea
subjects affected / exposed	7 / 108 (6.48%)	67 / 346 (19.36%)	65 / 111 (58.56%)
occurrences all number	7	69	65
Dental caries
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Dyspepsia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	2 / 111 (1.80%)
occurrences all number	0	1	2
Dysphagia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	1 / 111 (0.90%)
occurrences all number	0	1	1
Gastritis
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	2 / 111 (1.80%)
occurrences all number	0	0	2
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 108 (1.85%)	14 / 346 (4.05%)	3 / 111 (2.70%)
occurrences all number	2	14	3
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	18 / 346 (5.20%)	0 / 111 (0.00%)
occurrences all number	0	18	0
Haemorrhoids
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Haemorrhoids thrombosed
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Ileus
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Nausea
subjects affected / exposed	23 / 108 (21.30%)	113 / 346 (32.66%)	63 / 111 (56.76%)
occurrences all number	23	114	63
Oesophagitis
subjects affected / exposed	1 / 108 (0.93%)	6 / 346 (1.73%)	5 / 111 (4.50%)
occurrences all number	1	6	5
Palatal disorder
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Pancreatitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Salivary hypersecretion
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Rectal ulcer
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Salivary gland calculus
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Proctalgia
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Stomatitis
subjects affected / exposed	10 / 108 (9.26%)	115 / 346 (33.24%)	87 / 111 (78.38%)
occurrences all number	10	118	87
Tongue haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Tooth disorder
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Toothache
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Vomiting
subjects affected / exposed	9 / 108 (8.33%)	50 / 346 (14.45%)	44 / 111 (39.64%)
occurrences all number	9	50	44
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Hepatic failure
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	4	0
Hepatic steatosis
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	38 / 108 (35.19%)	144 / 346 (41.62%)	49 / 111 (44.14%)
occurrences all number	38	144	49
Acne
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Decubitus ulcer
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Dermatitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Dermatitis bullous
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Dermatitis contact
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences all number	1	0	0
Dry skin
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Epidermolysis
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Erythema
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	1	0	1
Hyperhidrosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Night sweats
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Petechiae
subjects affected / exposed	1 / 108 (0.93%)	5 / 346 (1.45%)	0 / 111 (0.00%)
occurrences all number	1	5	0
Pruritus
subjects affected / exposed	2 / 108 (1.85%)	26 / 346 (7.51%)	6 / 111 (5.41%)
occurrences all number	2	26	6
Rash
subjects affected / exposed	0 / 108 (0.00%)	5 / 346 (1.45%)	1 / 111 (0.90%)
occurrences all number	0	7	2
Rash erythematous
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Skin ulcer
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Solar lentigo
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Urticaria
subjects affected / exposed	2 / 108 (1.85%)	27 / 346 (7.80%)	5 / 111 (4.50%)
occurrences all number	2	27	5
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 108 (0.00%)	5 / 346 (1.45%)	1 / 111 (0.90%)
occurrences all number	0	5	1
Chronic kidney disease
subjects affected / exposed	0 / 108 (0.00%)	13 / 346 (3.76%)	2 / 111 (1.80%)
occurrences all number	0	14	2
Haematuria
subjects affected / exposed	2 / 108 (1.85%)	12 / 346 (3.47%)	4 / 111 (3.60%)
occurrences all number	2	12	4
Nocturia
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Pollakiuria
subjects affected / exposed	1 / 108 (0.93%)	4 / 346 (1.16%)	0 / 111 (0.00%)
occurrences all number	1	5	0
Urinary incontinence
subjects affected / exposed	1 / 108 (0.93%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	1	1	0
Urinary retention
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Urethral haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Endocrine disorders
Cushingoid
subjects affected / exposed	0 / 108 (0.00%)	4 / 346 (1.16%)	0 / 111 (0.00%)
occurrences all number	0	4	0
Hyperthyroidism
subjects affected / exposed	0 / 108 (0.00%)	16 / 346 (4.62%)	1 / 111 (0.90%)
occurrences all number	0	16	1
Hypothyroidism
subjects affected / exposed	3 / 108 (2.78%)	17 / 346 (4.91%)	0 / 111 (0.00%)
occurrences all number	3	17	0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Arthralgia
subjects affected / exposed	0 / 108 (0.00%)	5 / 346 (1.45%)	0 / 111 (0.00%)
occurrences all number	0	6	0
Back pain
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Bone pain
subjects affected / exposed	4 / 108 (3.70%)	84 / 346 (24.28%)	5 / 111 (4.50%)
occurrences all number	4	85	5
Exostosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Joint ankylosis
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences all number	1	0	0
Joint swelling
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Muscle spasms
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Muscular weakness
subjects affected / exposed	5 / 108 (4.63%)	25 / 346 (7.23%)	4 / 111 (3.60%)
occurrences all number	5	25	4
Musculoskeletal stiffness
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Myalgia
subjects affected / exposed	1 / 108 (0.93%)	8 / 346 (2.31%)	1 / 111 (0.90%)
occurrences all number	1	8	1
Rhabdomyolysis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Sacroiliitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Sjogren's syndrome
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Soft tissue necrosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Infections and infestations
Abdominal infection
subjects affected / exposed	1 / 108 (0.93%)	13 / 346 (3.76%)	8 / 111 (7.21%)
occurrences all number	1	13	8
Acarodermatitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Atypical pneumonia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Bronchitis
subjects affected / exposed	6 / 108 (5.56%)	30 / 346 (8.67%)	4 / 111 (3.60%)
occurrences all number	6	30	4
Cellulitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Clostridial infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Clostridium difficile infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	2 / 111 (1.80%)
occurrences all number	0	1	2
Conjunctivitis
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Cutaneous mucormycosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Cytomegalovirus infection reactivation
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	1 / 111 (0.90%)
occurrences all number	0	1	1
Device related infection
subjects affected / exposed	3 / 108 (2.78%)	53 / 346 (15.32%)	23 / 111 (20.72%)
occurrences all number	3	55	23
Enterobacter sepsis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Erysipelas
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Escherichia bacteraemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Escherichia infection
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Escherichia sepsis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Encephalitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Enterococcal infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Escherichia urinary tract infection
subjects affected / exposed	1 / 108 (0.93%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	1	1	0
Eye infection
subjects affected / exposed	3 / 108 (2.78%)	7 / 346 (2.02%)	0 / 111 (0.00%)
occurrences all number	3	8	0
Folliculitis
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Fungal skin infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Hepatitis A
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Herpes simplex
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Herpes virus infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Human herpesvirus 6 infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Influenza
subjects affected / exposed	0 / 108 (0.00%)	4 / 346 (1.16%)	0 / 111 (0.00%)
occurrences all number	0	4	0
Infection
subjects affected / exposed	0 / 108 (0.00%)	6 / 346 (1.73%)	1 / 111 (0.90%)
occurrences all number	0	6	1
Klebsiella bacteraemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Klebsiella infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Labyrinthitis
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences all number	1	0	0
Laryngitis
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Neutropenic sepsis
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Meningitis viral
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Mucosal infection
subjects affected / exposed	2 / 108 (1.85%)	42 / 346 (12.14%)	23 / 111 (20.72%)
occurrences all number	2	42	23
Nasopharyngitis
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Neutropenic infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Oesophageal candidiasis
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Oral candidiasis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Oropharyngeal candidiasis
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Otitis media
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Parotitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Pharyngitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Pneumonia
subjects affected / exposed	0 / 108 (0.00%)	36 / 346 (10.40%)	5 / 111 (4.50%)
occurrences all number	0	37	5
Parainfluenzae virus infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Proteus infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Pseudomonal bacteraemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Pseudomonal sepsis
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Rash pustular
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Sinusitis
subjects affected / exposed	2 / 108 (1.85%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	2	2	0
Skin infection
subjects affected / exposed	5 / 108 (4.63%)	38 / 346 (10.98%)	4 / 111 (3.60%)
occurrences all number	5	38	4
Soft tissue infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Staphylococcal bacteraemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Staphylococcal infection
subjects affected / exposed	0 / 108 (0.00%)	2 / 346 (0.58%)	0 / 111 (0.00%)
occurrences all number	0	2	0
Staphylococcal sepsis
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Streptococcal bacteraemia
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Sepsis
subjects affected / exposed	0 / 108 (0.00%)	0 / 346 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	0	1
Tooth infection
subjects affected / exposed	1 / 108 (0.93%)	10 / 346 (2.89%)	0 / 111 (0.00%)
occurrences all number	1	10	0
Subcutaneous abscess
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Systemic candida
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Urinary tract infection
subjects affected / exposed	9 / 108 (8.33%)	52 / 346 (15.03%)	14 / 111 (12.61%)
occurrences all number	9	53	14
Urinary tract infection bacterial
subjects affected / exposed	1 / 108 (0.93%)	0 / 346 (0.00%)	0 / 111 (0.00%)
occurrences all number	1	0	0
Vascular device infection
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Vulval abscess
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	4 / 108 (3.70%)	27 / 346 (7.80%)	8 / 111 (7.21%)
occurrences all number	4	27	8
Dehydration
subjects affected / exposed	2 / 108 (1.85%)	8 / 346 (2.31%)	0 / 111 (0.00%)
occurrences all number	2	8	0
Diabetes mellitus
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Fluid overload
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Gout
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	1 / 111 (0.90%)
occurrences all number	0	4	1
Hyperglycaemia
subjects affected / exposed	29 / 108 (26.85%)	152 / 346 (43.93%)	25 / 111 (22.52%)
occurrences all number	29	154	25
Hyperkalaemia
subjects affected / exposed	11 / 108 (10.19%)	71 / 346 (20.52%)	10 / 111 (9.01%)
occurrences all number	11	71	10
Hypernatraemia
subjects affected / exposed	0 / 108 (0.00%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	0	3	0
Hypoalbuminaemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Hypocalcaemia
subjects affected / exposed	2 / 108 (1.85%)	3 / 346 (0.87%)	0 / 111 (0.00%)
occurrences all number	2	3	0
Hypokalaemia
subjects affected / exposed	3 / 108 (2.78%)	19 / 346 (5.49%)	5 / 111 (4.50%)
occurrences all number	4	24	5
Hypomagnesaemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0
Hyponatraemia
subjects affected / exposed	20 / 108 (18.52%)	121 / 346 (34.97%)	29 / 111 (26.13%)
occurrences all number	20	121	29
Hypophosphataemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 346 (0.29%)	0 / 111 (0.00%)
occurrences all number	0	1	0

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Were there any global substantial amendments to the protocol? Yes

20 Apr 2018

Administrative changes: Change of principal investigator in center Hannover, Closure of study center Berlin (no recruitment), Registration of trial in ClinicalTrials.gov (NCT02531841) Clarification with reference to in-/exclusion criteria: • Addition of randomization criterion no. 4: “Exclusion criterion no. 6 not applicable for re-check for randomization” • Additional wording in randomization criterion no. 1: “Sufficient stem cell harvest (≥ 3 x 106 CD34+ cells/kg of body weight)” • Additional wording in exclusion criterion no. 6: “Only applicable for patient inclusion (registration) not applicable for re-check for randomization” • Correction of contents regarding the contraception time period of female and male patients on the basis of three SmPCs Sample size calculation: Increase of • recruitment period due to increase of number of patients enrolled • number of patients, that need to be recruited to obtain the originally planned number of 220 patients, that were to be randomized Adaption of figures and timelines: • Addition of specification “for evaluation of primary endpoint” regarding trial duration and time table Adaption of involved number of sites and countries: • Number of sites increased and the participating countries changed Adaption in flow chart: • Specification of response statement: “Whole brain MRI and response statement according to IPCG criteria” • More detailed timelines for RA III in case of postponement of consolidation therapy • Addition of more precise time period recommended for FU visits during year 3-5 and after year 5 Addition of special treatment recommendations regarding the Induction treatment phase. A special “pregnancy form”, which must be used replaced the former so called “SAE reporting form”. Detailed explanation was added regarding storage and use of stem cells. Improved wording regarding documentation and reporting of AEs and SAEs. Explanation regarding the handling of biomaterial was added.

14 Jun 2018

Additional demand of ethics committee to substantial amendment 01: Change in wording in Patient Informed Consent (PIC), version V03, section 12 regarding the notification of health damages which could have occurred as a result of the clinical study. Furthermore, a change in wording regarding documentation and reporting of AEs (section 10.1.2): “AEs must be documented … until day 60 after last administration of study medication randomization. If patient could not be randomized, AE documentation and reporting should be made until day 60 after last administration of study medication”.

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

http://www.ncbi.nlm.nih.gov/pubmed/27098429

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High-dose chemotherapy and autologous stem cell transplant or consolidating conventional chemotherapy in primary CNS lymphoma - randomized phase III trial

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Primary: Progression-free survival (FAS)

Primary: Progression-free survival (FAS)

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Clinical trials

Clinical Trial Results: High-dose chemotherapy and autologous stem cell transplant or consolidating conventional chemotherapy in primary CNS lymphoma - randomized phase III trial

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression-free survival (FAS)

Primary: Progression-free survival (FAS)

Secondary: Overall survival (FAS)

Secondary: Overall survival (FAS)

Secondary: Relapse rate

Secondary: Relapse rate

Secondary: Non Relapse Mortality (FAS)

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Secondary: Quality of life EORTC QLQ-C30: 1 year follow-up

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Secondary: Quality of life EORTC QLQ-C30: EOT change from screening

Secondary: Quality of life EORTC QLQ-C30: EOT change from screening

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Clinical Trial Results:
High-dose chemotherapy and autologous stem cell transplant or consolidating conventional chemotherapy in primary CNS lymphoma - randomized phase III trial