Clinical Trial Page

Clinical Trial Results:
Phase III multicentre open-label randomised study of ICE plus Rituximab (R-ICE) versus DHAP plus Rituximab (R-DHAP) in previously treated patients with CD 20 positive diffuse large B-cell lymphoma, eligible for transplantation followed by randomised maintenance treatment with Rituximab

Summary
EudraCT number	2004-002103-32
Trial protocol	IE
Global end of trial date	16 Jan 2014

Results information
Results version number	v1(current)
This version publication date	12 May 2018
First version publication date	12 May 2018
Other versions
Summary report(s)	CORAL_SUMMARY OF RESULTS

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

Collapse all Expand all

Trial information

Sponsor protocol code

50-03B

ISRCTN number

-

US NCT number

-

WHO universal trial number (UTN)

-

Sponsor organisation name

LYSARC

Sponsor organisation address

Centre Hospitalier Lyon-Sud - Secteur Sainte Eugénie - Pavillon 6D, PIERRE-BENITE, France, 69495

Public contact

Julie Assémat, LYSARC, 33 0472669333, julie.assemat@lysarc.org

Scientific contact

Pr Christian Gisselbrecht, LYSA, christian.gisselbrecht@gmail.com

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

No

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

No

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

No

Analysis stage

Final

Date of interim/final analysis

24 Nov 2010

Is this the analysis of the primary completion data?

Yes

Primary completion date

21 Oct 2008

Global end of trial reached?

Yes

Global end of trial date

16 Jan 2014

Was the trial ended prematurely?

No

Main objective of the trial

The main objective of the induction therapy is to evaluate the efficacy and safety of ICE plus Rituximab (R-ICE) in comparison with DHAP plus Rituximab (R-DHAP) in previously treated patients with CD20 positive diffuse large B cell lymphoma eligibale for autologous transplantation The objective of the maintenance therapy is to evaluate the efficacy and safety of Rituximab maintenance therapy after transplantation

Protection of trial subjects

If a patient does not respond, relapses or has progressive disease, every center was free to initiate further treatment according to local guidelines.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

24 Jul 2003

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Ireland: 4

Country: Number of subjects enrolled

Australia: 42

Country: Number of subjects enrolled

Belgium: 31

Country: Number of subjects enrolled

Czech Republic: 36

Country: Number of subjects enrolled

France: 128

Country: Number of subjects enrolled

Germany: 111

Country: Number of subjects enrolled

Israel: 13

Country: Number of subjects enrolled

New Zealand: 16

Country: Number of subjects enrolled

Switzerland: 24

Country: Number of subjects enrolled

Sweden: 13

Country: Number of subjects enrolled

United Kingdom: 50

Country: Number of subjects enrolled

United States: 9

Worldwide total number of subjects

477

EEA total number of subjects

373

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

460

From 65 to 84 years

17

85 years and over

0

Subject disposition

Recruitment details

Recruitment period from January 2003 until mid/end 2008

Screening details

- Patient with histologically proven, CD 20+ diffuse large B cell lymphoma in 1st relapse afterCR, less than PR or partial response to first line treatment - Aged from 18 to 65 years, inclusive - Eligible for transplant - Previously treated with chemotherapy regimen containing anthracyclines with or without rituximab - ECOG performance status

Period 1 title

Induction

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

R-ICE

Arm description

-

Arm type

standard

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

375mg/m2

R-DHAP

Arm description

-

Arm type

standard

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

375mg/m2

Number of subjects in period 1	R-ICE	R-DHAP
Started	243	234
Completed	205	196
Not completed	38	38
Protocol deviation	3	1
Lack of efficacy	20	24
death	4	6
unknown	2	1
Adverse event, non-fatal	7	4
Consent withdrawn by subject	2	2

Period 2 title

Consolidation

Is this the baseline period?

No

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

BEAM + ASCT (R-ICE)

Arm description

Consolidation treatment after R-ICE

Arm type

consolidation

Investigational medicinal product name

No investigational medicinal product assigned in this arm

BEAM + ASCT (R-DHAP)

Arm description

Consolidation treatment after R-DHAP

Arm type

consolidation

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	BEAM + ASCT (R-ICE)	BEAM + ASCT (R-DHAP)
Started	205	196
Completed	116	126
Not completed	89	70
Protocol deviation	1	-
Lack of efficacy	74	49
death	3	2
unknown	10	11
Adverse event, non-fatal	-	6
Consent withdrawn by subject	1	2

Period 3 title

Maintenance

Is this the baseline period?

No

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Observation

Arm description

-

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Rituximab

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

375mg/m2

Number of subjects in period 3	Observation	Rituximab
Started	120	122
Completed	41	30
Not completed	81	92
Transferred to other arm/group	-	2
Lack of efficacy	38	35
death	39	42
Adverse event, serious fatal	1	3
Adverse event, non-fatal	-	3
Consent withdrawn by subject	3	6
Lost to follow-up	-	1
Joined	2	0
Transferred in from other group/arm	2	-

Baseline characteristics

Reporting group title

R-ICE

Reporting group description

-

Reporting group title

R-DHAP

Reporting group description

-

Reporting group values	R-ICE	R-DHAP	Total
Number of subjects	243	234	477
Age categorical
Units: Subjects
In utero			0
Preterm newborn infants (gestational age < 37 wks)			0
Newborns (0-27 days)			0
Infants and toddlers (28 days-23 months)			0
Children (2-11 years)			0
Adolescents (12-17 years)			0
Adults (18-64 years)			0
From 65-84 years			0
85 years and over			0
Age continuous
R-ICE (N=242): mean = 50.7 median = 54.0 min = 19; max = 65 R-DHAP (N=234) mean = 52.3 median = 55.0 min = 19; max = 65
Units: years
median (full range (min-max))	54 (19 to 65)	55 (19 to 65)	-
Gender categorical
Units: Subjects
Female	87	87	174
Male	156	147	303

Subject analysis set title

Induction Full Analysis Set

Subject analysis set type

Full analysis

Subject analysis set description

(following the intent-to-treat principle) refers to all randomized patients regardless they have received study treatment or not: 477 patients analyzed according the therapy they were randomized to receive (243 in R-ICE arm and 234 in RDHAP arm).

Subject analysis set title

Induction Intent To Treat Population

Subject analysis set type

Intention-to-treat

Subject analysis set description

refers to patients receiving at least one injection of study treatment, regardless the quantity injected: 469 patients analyzed according the therapy they were randomized to receive (239 in R-ICE arm and 230 in RDHAP arm).

Subject analysis set title

Induction Safety population

Subject analysis set type

Safety analysis

Subject analysis set description

refers to patients receiving at least one injection of study treatment: 469 patients analyzed according the therapy they actually received (239 in R-ICE arm and 230 in R-DHAP arm).

Subject analysis set title

Maintenance Intent To Treat Population

Subject analysis set type

Intention-to-treat

Subject analysis set description

refers to all patients formally randomized in the 2nd part of the study: 242 patients analyzed according the therapy they were randomized to receive (122 in rituximab arm and 120 in observation arm).

Subject analysis set title

Maintenance Safety Population

Subject analysis set type

Safety analysis

Subject analysis set description

refers to all patients formally randomized in the 2nd part of the study and have received at least one dose of rituximab or have only been observed, and have at least one maintenance follow-up assessment: 235 patients analyzed according the therapy they actually received, i.e. patient will be included in rituximab arm if he/she had received at least one dose of rituximab during any maintenance visit otherwise, he/she will be included in observation arm (thus, 116 in rituximab arm and 119 in observation arm).

Subject analysis sets values	Induction Full Analysis Set	Induction Intent To Treat Population	Induction Safety population	Maintenance Intent To Treat Population	Maintenance Safety Population
Number of subjects	477	469	469	242	235
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age continuous
R-ICE (N=242): mean = 50.7 median = 54.0 min = 19; max = 65 R-DHAP (N=234) mean = 52.3 median = 55.0 min = 19; max = 65
Units: years
median (full range (min-max))	54 (19 to 65)
Gender categorical
Units: Subjects
Female
Male

End points

Reporting group title

R-ICE

Reporting group description

-

Reporting group title

R-DHAP

Reporting group description

-

Reporting group title

BEAM + ASCT (R-ICE)

Reporting group description

Consolidation treatment after R-ICE

Reporting group title

BEAM + ASCT (R-DHAP)

Reporting group description

Consolidation treatment after R-DHAP

Reporting group title

Observation

Reporting group description

-

Reporting group title

Rituximab

Reporting group description

-

Subject analysis set title

Induction Full Analysis Set

Subject analysis set type

Full analysis

Subject analysis set description

(following the intent-to-treat principle) refers to all randomized patients regardless they have received study treatment or not: 477 patients analyzed according the therapy they were randomized to receive (243 in R-ICE arm and 234 in RDHAP arm).

Subject analysis set title

Induction Intent To Treat Population

Subject analysis set type

Intention-to-treat

Subject analysis set description

refers to patients receiving at least one injection of study treatment, regardless the quantity injected: 469 patients analyzed according the therapy they were randomized to receive (239 in R-ICE arm and 230 in RDHAP arm).

Subject analysis set title

Induction Safety population

Subject analysis set type

Safety analysis

Subject analysis set description

refers to patients receiving at least one injection of study treatment: 469 patients analyzed according the therapy they actually received (239 in R-ICE arm and 230 in R-DHAP arm).

Subject analysis set title

Maintenance Intent To Treat Population

Subject analysis set type

Intention-to-treat

Subject analysis set description

refers to all patients formally randomized in the 2nd part of the study: 242 patients analyzed according the therapy they were randomized to receive (122 in rituximab arm and 120 in observation arm).

Subject analysis set title

Maintenance Safety Population

Subject analysis set type

Safety analysis

Subject analysis set description

refers to all patients formally randomized in the 2nd part of the study and have received at least one dose of rituximab or have only been observed, and have at least one maintenance follow-up assessment: 235 patients analyzed according the therapy they actually received, i.e. patient will be included in rituximab arm if he/she had received at least one dose of rituximab during any maintenance visit otherwise, he/she will be included in observation arm (thus, 116 in rituximab arm and 119 in observation arm).

Primary: Mobilization Adjusted Response Rate after induction chemotherapy

End point title

Mobilization Adjusted Response Rate after induction chemotherapy

End point description

MARR = overall response rate (ORR) (CR/CRu/PR) adjusted with successful mobilization at the end of 2 and/or 3 cycles of induction chemotherapy treatment before high-dose chemotherapy and autologous transplantation Responses are defined, according to Cheson et al (6), response after 3 cycles of treatment will be evaluated by an external expert committee after recommendation from the steering committee (CR, CRu, PR, SD, PD and relpased disease for patients in CR or CRu).

End point type

Primary

End point timeframe

It will be a composite endpoint including response rate and success of mobilization of stem cells. Response rate after 3 cycles of chemotherapy and at the end of treatment.

End point values	R-ICE	R-DHAP
Number of subjects analysed	239 ^[1]	230 ^[2]
Units: percent
number (confidence interval 95%)	51.5 (44.9 to 58.0)	56.5 (49.8 to 63.0)

Notes
[1] - Induction ITT set R-ICE arm
[2] - Induction ITT arm R-CHOP arm

Primary criterion - Induction

Comparison groups

R-DHAP v R-ICE

Number of subjects included in analysis

469

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.272

Method

Chi-squared

Parameter type

OR rates difference

Point estimate

-5.1

Confidence interval

level

95%

sides

2-sided

lower limit

-14.1

upper limit

4

Primary: Event free survival after transplant

End point title

Event free survival after transplant

End point description

Events are defined as follows:  - Progression of the lymphoma during or after treatment for patients who achieved a response qualified as stable disease or PR,  - Relapse for CR and CRu patients,  - Institution of a new treatment for the lymphoma  - Death from any cause, without progression. Event-Free Survival (EFS) is measured from date of 2nd randomization to date of first event on the Maintenance ITT population.

End point type

Primary

End point timeframe

EFS at 2-years in months

End point values	Observation	Rituximab
Number of subjects analysed	120	122
Units: percent
number (confidence interval 95%)	59.3 (49.8 to 67.5)	59.2 (49.7 to 67.5)

Primary criterion - Maintenance

Comparison groups

Observation v Rituximab

Number of subjects included in analysis

242

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

= 0.7435

Method

Logrank

Confidence interval

Notes
[3] - The event free survival post transplant will be analyzed using the stratified log rank test.

Adverse events

Timeframe for reporting adverse events

All Adverse Events (AE) occurring during the treatment period and until 30 days after the end of the last cycle of treatment or last dose of Rituximab will be recorded on the toxicity forms

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17

Reporting group title

R-ICE

Reporting group description

-

Reporting group title

R-DHAP

Reporting group description

-

Serious adverse events	R-ICE	R-DHAP
Total subjects affected by serious adverse events
subjects affected / exposed	66 / 239 (27.62%)	84 / 234 (35.90%)
number of deaths (all causes)	126	15
number of deaths resulting from adverse events	9	15
Vascular disorders
Thrombosis
Additional description: All vascular disorders are reported in the table below
subjects affected / exposed	2 / 239 (0.84%)	2 / 234 (0.85%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Hepatectomy
subjects affected / exposed	0 / 239 (0.00%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
Additional description: All these neoplasms are reported in the table below
subjects affected / exposed	4 / 239 (1.67%)	3 / 234 (1.28%)
occurrences causally related to treatment / all	2 / 4	1 / 3
deaths causally related to treatment / all	2 / 2	1 / 1
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 239 (0.00%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Social circumstances
social stay hospitalisation
subjects affected / exposed	0 / 239 (0.00%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
pyrexia
Additional description: All general disorders are reported in the table below
subjects affected / exposed	5 / 239 (2.09%)	6 / 234 (2.56%)
occurrences causally related to treatment / all	0 / 5	1 / 6
deaths causally related to treatment / all	0 / 0	1 / 1
Psychiatric disorders
Depression
Additional description: All psychiatric disorders are reported in the table below
subjects affected / exposed	1 / 239 (0.42%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Subdural haematoma
Additional description: All these complications are reported in the table below
subjects affected / exposed	2 / 239 (0.84%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	0 / 239 (0.00%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
cardiac failure
Additional description: All cardiac disorders are reported in the able below
subjects affected / exposed	6 / 239 (2.51%)	5 / 234 (2.14%)
occurrences causally related to treatment / all	2 / 6	1 / 5
deaths causally related to treatment / all	2 / 2	1 / 1
Blood and lymphatic system disorders
Neutropenia
Additional description: All blood and lymphatic system disorders are reported in the table below
subjects affected / exposed	11 / 239 (4.60%)	16 / 234 (6.84%)
occurrences causally related to treatment / all	0 / 11	2 / 16
deaths causally related to treatment / all	0 / 0	2 / 2
Respiratory, thoracic and mediastinal disorders
respiratory failure
Additional description: All respiratory, thoracic and mediastinal disorders are reported in the table below
subjects affected / exposed	6 / 239 (2.51%)	5 / 234 (2.14%)
occurrences causally related to treatment / all	2 / 6	5 / 5
deaths causally related to treatment / all	2 / 2	5 / 5
Nervous system disorders
Cerebrovascular accident
Additional description: All nervous system disorders are reported in the table below
subjects affected / exposed	4 / 239 (1.67%)	13 / 234 (5.56%)
occurrences causally related to treatment / all	0 / 4	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
deafness
Additional description: All ear and labyrinth disorders are reported in the table below
subjects affected / exposed	1 / 239 (0.42%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Gastrointestinal disorder
Additional description: All gastrointestinal disorders are reported in the table below
subjects affected / exposed	10 / 239 (4.18%)	19 / 234 (8.12%)
occurrences causally related to treatment / all	0 / 10	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Renal failure
Additional description: All renal and urinary disorders are reported in the table below
subjects affected / exposed	2 / 239 (0.84%)	12 / 234 (5.13%)
occurrences causally related to treatment / all	0 / 2	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
hepatitis
Additional description: All hepatobiliary disorders are reported in the table below
subjects affected / exposed	3 / 239 (1.26%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Skin reaction
subjects affected / exposed	0 / 239 (0.00%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
back pain
Additional description: All these disorders are reported in the table below
subjects affected / exposed	1 / 239 (0.42%)	2 / 234 (0.85%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
Additional description: All metabolism and nutrition disorders are reported in the table below
subjects affected / exposed	2 / 239 (0.84%)	6 / 234 (2.56%)
occurrences causally related to treatment / all	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Neutropenic sepsis
Additional description: All SAE related to infections and infestations are reported in the table below
subjects affected / exposed	46 / 239 (19.25%)	55 / 234 (23.50%)
occurrences causally related to treatment / all	3 / 46	4 / 55
deaths causally related to treatment / all	3 / 3	4 / 4

Frequency threshold for reporting non-serious adverse events: 0.7%

Non-serious adverse events	R-ICE	R-DHAP
Total subjects affected by non serious adverse events
subjects affected / exposed	154 / 239 (64.44%)	172 / 234 (73.50%)
Vascular disorders
Thrombosis
Additional description: All vascular disorders are reported in the table below
subjects affected / exposed	6 / 239 (2.51%)	7 / 234 (2.99%)
occurrences all number	6	7
Surgical and medical procedures
Hepatectomy
subjects affected / exposed	0 / 239 (0.00%)	1 / 234 (0.43%)
occurrences all number	0	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour lysis syndrome
Additional description: All these neoplasms are reported in the table below
subjects affected / exposed	4 / 239 (1.67%)	7 / 234 (2.99%)
occurrences all number	4	7
Immune system disorders
Drug hypersensitivity
Additional description: All immune system disorders are reported in the table below
subjects affected / exposed	4 / 239 (1.67%)	5 / 234 (2.14%)
occurrences all number	4	5
Social circumstances
Social stay hospitalisation
subjects affected / exposed	0 / 239 (0.00%)	1 / 234 (0.43%)
occurrences all number	0	1
General disorders and administration site conditions
Pyrexia
Additional description: All general disorders are reported in the table below
subjects affected / exposed	40 / 239 (16.74%)	51 / 234 (21.79%)
occurrences all number	40	51
Psychiatric disorders
depression
Additional description: All psychiatric disorders are reported in the table below
subjects affected / exposed	1 / 239 (0.42%)	3 / 234 (1.28%)
occurrences all number	1	3
Injury, poisoning and procedural complications
drug toxicity
Additional description: All these complications are reported in the table below
subjects affected / exposed	2 / 239 (0.84%)	2 / 234 (0.85%)
occurrences all number	2	2
Investigations
Blood creatinine increased
Additional description: All investigations are reported in the table below
subjects affected / exposed	12 / 239 (5.02%)	17 / 234 (7.26%)
occurrences all number	12	17
Cardiac disorders
cadiac failure
Additional description: All cardiac disorders are reported in the table below
subjects affected / exposed	7 / 239 (2.93%)	6 / 234 (2.56%)
occurrences all number	7	6
Blood and lymphatic system disorders
neutropenia
Additional description: All blood and lymphatic disorders are reported in the table below
subjects affected / exposed	64 / 239 (26.78%)	116 / 234 (49.57%)
occurrences all number	64	116
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
Additional description: All respiratory, thoracic and mediastinal disorders are reported in the table below
subjects affected / exposed	10 / 239 (4.18%)	11 / 234 (4.70%)
occurrences all number	10	11
Nervous system disorders
Cerebrovascular accident
Additional description: All nervous system disorders are reported in the table below
subjects affected / exposed	7 / 239 (2.93%)	19 / 234 (8.12%)
occurrences all number	7	19
Ear and labyrinth disorders
deafness
Additional description: All ear and labyrinth disorders are reported in the table below
subjects affected / exposed	2 / 239 (0.84%)	4 / 234 (1.71%)
occurrences all number	2	4
Gastrointestinal disorders
Vomiting
Additional description: All GI disorders are reported in the table below
subjects affected / exposed	33 / 239 (13.81%)	65 / 234 (27.78%)
occurrences all number	33	65
Hepatobiliary disorders
hepatitis
Additional description: All hepatobiliary disorders are reported in the table below
subjects affected / exposed	3 / 239 (1.26%)	5 / 234 (2.14%)
occurrences all number	3	5
Renal and urinary disorders
renal failure acute
Additional description: All renal and urinary disorders are reported in the table below
subjects affected / exposed	2 / 239 (0.84%)	21 / 234 (8.97%)
occurrences all number	2	21
Skin and subcutaneous tissue disorders
Skin reaction
Additional description: All skin and subcutaneous tissue disorders are reported in the table below
subjects affected / exposed	2 / 239 (0.84%)	1 / 234 (0.43%)
occurrences all number	2	1
Musculoskeletal and connective tissue disorders
Bone pain
Additional description: All musculoskeletal and connective tissue disorders are reported in the table below
subjects affected / exposed	2 / 239 (0.84%)	4 / 234 (1.71%)
occurrences all number	2	4
Metabolism and nutrition disorders
hypokaliemia
Additional description: All metabolism and nutrition disorders are reported in the table below
subjects affected / exposed	11 / 239 (4.60%)	40 / 234 (17.09%)
occurrences all number	11	40
Infections and infestations
Infection
Additional description: All infections and infestations are reported in the table below
subjects affected / exposed	135 / 239 (56.49%)	166 / 234 (70.94%)
occurrences all number	135	166

More information

Were there any global substantial amendments to the protocol? Yes

05 Jul 2007

La première analyse de sécurité et l’analyse intermédiaire réalisées dans le cadre de l’étude citée en référence ont montré que le nombre de randomisations prévues dans la deuxième partie de l’étude ne serait pas atteint. Le taux de sorti d’essai avant la deuxième randomisation atteignant 50 %. L’augmentation du recrutement à 480 patients est nécessaire pour atteindre l’objectif de la deuxième partie de l’étude. En second lieu, l’amendement prend en compte le changement du Résumé des Caractéristiques du Produit du Mabthera mis à jour au 12 janvier 2007.

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

3

Subscribe