Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in MALT Lymphoma

• Sponsor: International Extranodal Lymphoma Study Group (IELSG) (Other)
• Overall Status: Completed
• CT.gov ID: NCT00210353
• Collaborator: (none)
• Enrollment: 454
• Locations: 75
• Arms: 3
• Duration (Months): 157.5
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Assess the therapeutic activity and safety of the combination of Chlorambucil and Rituximab in MALT lymphomas and determine whether the addition of Rituximab to Chlorambucil will improve the outcome of MALT lymphoma in comparison to treatment with Chlorambucil alone.

In April 2006, a third arm of treatment was added to compare the antitumor activity and safety of rituximab alone vs chlorambucil alone

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Mucosa-Associated Lymphoid Tissue	Drug: chlorambucil (drug); Drug: rituximab+chlorambucil; Drug: rituximab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 454 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter Randomized Trial of Chlorambucil Versus Chlorambucil Plus Rituximab Versus Rituximab in Extranodal Marginal Zone B-cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT Lymphoma)
• Study Start Date: Jan 1, 2003
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Feb 17, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ARM A chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment; two weeks rest; chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)	Drug: chlorambucil (drug); chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment, two weeks rest, chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)
Experimental: ARM B rituximab 375 mg/m2 iv, d1, d8, d15, d22 chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment two weeks rest chlorambucil 6 mg/m2 os daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle	Drug: rituximab+chlorambucil; rituximab 375 mg/m2 iv, d1, 8, 15, 22, chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment, ; two weeks rest; chlorambucil 6 mg/m2 os, daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle
Experimental: ARM C (Since April 2006) rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140	Drug: rituximab; rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140

Outcome Measures

Primary Outcome Measures

1. Event-free-survival (EFS) [5 years]

   Percentage of patients without events (failure of treatment or Death from any cause) after 5 years from trial registration

Secondary Outcome Measures

1. Complete and Partial Remission Rate - Percentage of Patients With Complete and Partial Response at the End of Treatment [End of treatment (after 24 weeks of therapy)]

   Response criteria were defined according to the NCI standardized response criteria for non-Hodgkin's lymphoma. Complete response. Disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms, if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Regression of all lymph nodes and nodal masses to normal (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm before therapy and to ≤ 1 cm for nodes that were 1.1-1.5 cm. Regression by more than 75% in the sum of the products of the greatest diameters). Partial response. Decrease by at least 50% in SPD of the six largest measurable lesions. It is not necessary for all lesions to have regressed to qualify for partial response, but no lesion should have progressed and no new lesion should appear. For primary gastric sites, response was based on GELA histologic grading system.

2. Response Duration (Time to Relapse or Progression) - Percentage of Patients in Continuous Remission at Five Years From Trial Registration [5 years]

   Response criteria were defined according to the NCI standardized response criteria for non-Hodgkin's lymphoma. Complete response (CR). Disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms, if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Regression of all lymph nodes and nodal masses to normal (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm before therapy and to ≤ 1 cm for nodes that were 1.1-1.5 cm. Regression by more than 75% in the sum of the products of the greatest diameters).

3. Progression-free-survival (PFS) [5 years]

   Percentage of patients without disease progression after 5 years from trial registration

4. Overall Survival [5 years]

   Percentage of patients alive after 5 years from trial registration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. histologically proven diagnosis of CD20-positive marginal zone B-cell lymphoma of MALT type arisen at any extranodal site

2. any stage (Ann Arbor I-IV)

3. either de novo, or relapsed disease following local therapy (including surgery, radiotherapy and antibiotics for H. pylori-positive gastric lymphoma)

4. no evidence of histologic transformation to a high grade lymphoma

5. measurable or evaluable disease

6. age > 18

7. life expectancy of at least 1 year

8. ECOG performance status 0-2

9. no prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer

10. no prior chemotherapy

11. no prior immunotherapy with any anti-CD20 monoclonal antibody

12. no prior radiotherapy in the last 6 weeks

13. no corticosteroids during the last 28 days, unless prednisone chronically administered at a dose <20 mg/day for indications other than lymphoma or lymphoma-related symptoms

14. no evidence of clinically significant cardiac disease, as defined by history of symptomatic ventricular arrhythmias, congestive heart failure or myocardial infarction within 12 months before study entry

15. no evidence of symptomatic central nervous system (CNS) disease

16. no impairment of bone marrow function (WBC >3.0x109/L, ANC >1.5x109/L, PLT

100x109/L), unless due to lymphoma involvement

1. no major impairment of renal function (serum creatinine <1,5x upper normal) or liver function (ASAT/ALAT <2,5 upper normal, total bilirubin <2,5x upper normal), unless due to lymphoma involvement

2. no evidence of active opportunistic infections

3. no known HIV infection

4. no active HBV and/or HCV infection

5. no pregnant or lactating status

6. appropriate contraceptive method in women of childbearing potential or men

7. absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

8. informed consent must be given according to national/local regulations before randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ACZA Campus Stuivenberg	Antwerpen		Belgium
2	AZ StJan	Brugge		Belgium
3	St Luc	Bruxelles		Belgium
4	ULB Hopital Erasme	Bruxelles		Belgium
5	CHNDRF	Charleroi		Belgium
6	Hospital St Joseph	Gilly		Belgium
7	UCL de Mont Godinne	Yvoir		Belgium
8	Centre Hospitalier de Blois	Blois		France
9	Hopital Avicenne	Bobigny		France
10	CHU	Dijon		France
11	Centre Hospitalier	Lens		France
12	CHRU Lille	Lille		France
13	Centre Hospitalier Lyon Sud	Lyon		France
14	Centre Leon Berard	Lyon		France
15	Institut Paoli Calmettes	Marseille		France
16	Hopital Arnold Villeneuve	Monpellier		France
17	CHU	Nancy		France
18	Centre R. Gauducheau	Nantes-St. Herblain		France
19	CHU Hotel Dieu	Nantes		France
20	Hopital Henri-Mondor	Paris		France
21	Hopital St Louis	Paris		France
22	Necker	Paris		France
23	Centre Henri Becquerel	Rouen		France
24	Spedali Civili	Brescia		Italy
25	Azienda ULSS 15 Alta Padovana	Cittadella		Italy
26	IST	Genova		Italy
27	IEO	Milano		Italy
28	INT	Milano		Italy
29	Humanitas	Milan		Italy
30	San Raffaele Hospital	Milan		Italy
31	Policlinico	Modena		Italy
32	Ospedale Civile	Piacenza		Italy
33	A.O. Bianchi-Melacrino-Morelli, Divisione di Ematologia	Reggio Calabria		Italy
34	Arcispedale S. Maria Nuova	Reggio Emilia		Italy
35	S. Eugenio	Rome		Italy
36	Università Cattolica Sacro Cuore	Rome		Italy
37	Università La Sapienza	Rome		Italy
38	Sassuolo GISL	Sassuolo		Italy
39	AOU Senese	Siena		Italy
40	A.O.U. San Giovanni Battista-Molinette, S.C. Ematologia 2	Torino		Italy	10134
41	Trani GISL	Trani		Italy
42	Ospedale di Circolo Fondazione Macchi	Varese		Italy
43	Policlinico GB Rossi	Verona		Italy
44	Clinic Hospital Universitari	Barcelona		Spain
45	Hopital Mataro'	Barcelona		Spain
46	Hopital Santa Creu i Sant Pau	Barcelona		Spain
47	University Hospital	Salamanca		Spain
48	Joan XXIII	Tarragona		Spain
49	IOSI	Bellinzona		Switzerland	6500
50	Aberdeen Royal Infirmary	Aberdeen		United Kingdom
51	Heartlands	Birmingham		United Kingdom
52	Victoria Hospital	Blackpool		United Kingdom
53	Royal Cornwall Hospital	Cornwall		United Kingdom
54	Darent Valley Hospital	Dartford		United Kingdom
55	Royal Devon &Exeter Healtcare NHS Trust	Devon		United Kingdom
56	Russels Hall Hospital	Dudley		United Kingdom
57	Western General Hospital	Edinburgh		United Kingdom
58	Medway Hospital	Gillingham		United Kingdom
59	Raigmore Hospital	Inverness		United Kingdom
60	Liverpool Royal Hospital	Liverpool		United Kingdom
61	University Hospital Aintree	Liverpool		United Kingdom
62	Barts & the London NHS Trust	London		United Kingdom
63	Royal Marsden NHS Foundation Trust	London		United Kingdom
64	St Georges	London		United Kingdom
65	Christie Hospital	Manchester		United Kingdom
66	Mount Vernon Hospital	Middlesex		United Kingdom
67	James Paget Hospital	Norfolk		United Kingdom
68	Queen Elisabeth	Norfolk		United Kingdom
69	Nottingham City Hospital	Nottingham		United Kingdom
70	John Radcliffe	Oxford		United Kingdom
71	Conquest Hospital	Saint Leonard On Sea		United Kingdom
72	Weston Park	Sheffield		United Kingdom
73	Southampton General Hospital	Southampton		United Kingdom
74	Sandwell General Hospital	West Bromwich		United Kingdom
75	Worchestershire Acute Hospital NHS Trust	Worcester		United Kingdom

Sponsors and Collaborators

• International Extranodal Lymphoma Study Group (IELSG)

Investigators

• Study Chair: Emanuele Zucca, MD, International Extranodal Lymphoma Study Group/Oncology Institute of Southern Switzerland. Bellinzona
• Study Chair: Emilio Montserrat, MD, Clinic Hospital Universitari, Hematology. Barcelona
• Study Chair: Catherine Thieblemont, MD, Centre Hospitalier Lyon Sud, Hematology. Lyon
• Study Chair: Giovanni Martinelli, MD, Hemato-oncology. European Oncology Institute. Milan
• Study Chair: Peter Johnson, MD, Oncology Unit. Southampton General Hospital. Southampton
• Study Chair: Maurizio Martelli, MD, Hematology. Università La Sapienza. Roma

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for more information about this study

Publications

None provided.

• Responsible Party: International Extranodal Lymphoma Study Group (IELSG)
• ClinicalTrials.gov Identifier: NCT00210353
• Other Study ID Numbers: IELSG19
• First Posted: Sep 21, 2005
• Last Update Posted: Jun 6, 2019
• Last Verified: Oct 1, 2018

• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell, Marginal Zone; Rituximab; Chlorambucil

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled from 10 January 2003 to 07 July 2010

Arm/Group Title	ARM A - Chlorambucil	ARM B - Rituximab + Chlorambucil	ARM C (Since April 2006) - Rituximab
Arm/Group Description	Chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment; two weeks rest; chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)	rituximab 375 mg/m2 iv, d1, d8, d15, d22 chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment two weeks rest chlorambucil 6 mg/m2 os daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle	Rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
Period Title: Overall Study
STARTED	151	152	151
COMPLETED	113	107	125
NOT COMPLETED	38	45	26

Baseline Characteristics

Arm/Group Title	ARM A - Chlorambucil	ARM B - Rituximab + Chlorambucil	ARM C (Since April 2006) - Rituximab	Total
Arm/Group Description	Chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment; two weeks rest; chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)	Rituximab 375 mg/m2 iv, d1, d8, d15, d22 Chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment two weeks rest chlorambucil 6 mg/m2 os daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle	Rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140	Total of all reporting groups
Overall Participants	131	132	138	401
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60	59.5	62.5	61
Sex: Female, Male (Count of Participants)
Female	62 47.3%	68 51.5%	74 53.6%	204 50.9%
Male	69 52.7%	64 48.5%	64 46.4%	197 49.1%
Region of Enrollment (participants) [Number]
Belgium	8 6.1%	5 3.8%	15 10.9%	28 7%
Italy	54 41.2%	52 39.4%	58 42%	164 40.9%
United Kingdom	18 13.7%	23 17.4%	19 13.8%	60 15%
France	39 29.8%	40 30.3%	41 29.7%	120 29.9%
Switzerland	3 2.3%	3 2.3%	5 3.6%	11 2.7%
Spain	9 6.9%	9 6.8%	0 0%	18 4.5%
Ann Arbor stage (Count of Participants)
Ann Arbor Stage > 2	53 40.5%	59 44.7%	63 45.7%	175 43.6%
Ann arbor stage ≤ 2	78 59.5%	73 55.3%	75 54.3%	226 56.4%
B-symptoms (Count of Participants)
Presence of B-symptoms	6 4.6%	20 15.2%	16 11.6%	42 10.5%
Absence of B symptoms	125 95.4%	112 84.8%	122 88.4%	359 89.5%
International Prognostic Index (IPI) risk (Count of Participants)
Low	79 60.3%	74 56.1%	76 55.1%	229 57.1%
Low-intermediate	25 19.1%	34 25.8%	35 25.4%	94 23.4%
Intermediate-high	23 17.6%	20 15.2%	25 18.1%	68 17%
High	3 2.3%	4 3%	2 1.4%	9 2.2%
NA	1 0.8%	0 0%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Event-free-survival (EFS)
Description	Percentage of patients without events (failure of treatment or Death from any cause) after 5 years from trial registration
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Evaluable patients

Arm/Group Title	ARM A - Chlorambucil	ARM B - Rituximab + Chlorambucil	ARM C (Since April 2006) - Rituximab
Arm/Group Description	Chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment; two weeks rest; chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)	Rituximab 375 mg/m2 iv, d1, d8, d15, d22 chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment two weeks rest chlorambucil 6 mg/m2 os daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle	Rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
Measure Participants	131	132	138
Number (95% Confidence Interval) [percentage of patients]	51	68	51

2. Secondary Outcome

Title	Complete and Partial Remission Rate - Percentage of Patients With Complete and Partial Response at the End of Treatment
Description	Response criteria were defined according to the NCI standardized response criteria for non-Hodgkin's lymphoma. Complete response. Disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms, if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Regression of all lymph nodes and nodal masses to normal (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm before therapy and to ≤ 1 cm for nodes that were 1.1-1.5 cm. Regression by more than 75% in the sum of the products of the greatest diameters). Partial response. Decrease by at least 50% in SPD of the six largest measurable lesions. It is not necessary for all lesions to have regressed to qualify for partial response, but no lesion should have progressed and no new lesion should appear. For primary gastric sites, response was based on GELA histologic grading system.
Time Frame	End of treatment (after 24 weeks of therapy)

Outcome Measure Data

Analysis Population Description

Evaluable patients

Arm/Group Title	ARM A - Chlorambucil	ARM B - Rituximab + Chlorambucil	ARM C (Since April 2006) - Rituximab
Arm/Group Description	Chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment; two weeks rest; chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)	Rituximab 375 mg/m2 iv, d1, d8, d15, d22 Chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment two weeks rest chlorambucil 6 mg/m2 os daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle	Rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
Measure Participants	131	132	138
Number (95% Confidence Interval) [percentage of patients]	85.5	94.7	78.3

3. Secondary Outcome

Title	Response Duration (Time to Relapse or Progression) - Percentage of Patients in Continuous Remission at Five Years From Trial Registration
Description	Response criteria were defined according to the NCI standardized response criteria for non-Hodgkin's lymphoma. Complete response (CR). Disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms, if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. Regression of all lymph nodes and nodal masses to normal (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm before therapy and to ≤ 1 cm for nodes that were 1.1-1.5 cm. Regression by more than 75% in the sum of the products of the greatest diameters).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Evaluable patients

Arm/Group Title	ARM A - Chlorambucil	ARM B - Rituximab + Chlorambucil	ARM C (Since April 2006) - Rituximab
Arm/Group Description	Chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment; two weeks rest; chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)	Rituximab 375 mg/m2 iv, d1, d8, d15, d22 chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment two weeks rest chlorambucil 6 mg/m2 os daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle	Rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
Measure Participants	131	132	138
Number (95% Confidence Interval) [percentage of patients]	70	79	66

4. Secondary Outcome

Title	Progression-free-survival (PFS)
Description	Percentage of patients without disease progression after 5 years from trial registration
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Evaluable Patients

Arm/Group Title	ARM A - Chlorambucil	ARM B - Rituximab + Chlorambucil	ARM C (Since April 2006) - Ritiximab
Arm/Group Description	Chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment; two weeks rest; chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)	Rituximab 375 mg/m2 iv, d1, d8, d15, d22 chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment two weeks rest chlorambucil 6 mg/m2 os daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle	rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
Measure Participants	131	132	138
Number (95% Confidence Interval) [percentage of patients]	59	72	57

5. Secondary Outcome

Title	Overall Survival
Description	Percentage of patients alive after 5 years from trial registration
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Evaluable Patients

Arm/Group Title	ARM A	ARM B	ARM C (Since April 2006)
Arm/Group Description	chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment; two weeks rest; chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles) chlorambucil (drug): chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment, two weeks rest, chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)	rituximab 375 mg/m2 iv, d1, d8, d15, d22 chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment two weeks rest chlorambucil 6 mg/m2 os daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle rituximab+chlorambucil: rituximab 375 mg/m2 iv, d1, 8, 15, 22, chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment, ; two weeks rest; chlorambucil 6 mg/m2 os, daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle	rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140 rituximab: rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
Measure Participants	131	132	138
Number (95% Confidence Interval) [percentage of patients]	89	90	92

Adverse Events

Time Frame	Seven years and eight months
Arm/Group Title	ARM A		ARM B		ARM C (Since April 2006)
Arm/Group Description	chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment; two weeks rest; chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles) chlorambucil (drug): chlorambucil 6 mg/m2 daily during the first 6 weeks of treatment, two weeks rest, chlorambucil 6 mg/m2 daily during the first two of a four weeks cycles (total of 4 cycles)		rituximab 375 mg/m2 iv, d1, d8, d15, d22 chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment two weeks rest chlorambucil 6 mg/m2 os daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle rituximab+chlorambucil: rituximab 375 mg/m2 iv, d1, 8, 15, 22, chlorambucil 6 mg/m2 os, daily during the first 6 weeks of treatment, ; two weeks rest; chlorambucil 6 mg/m2 os, daily during the first two of a four weeks cycles (total of 4 cycles) rituximab 375 mg/m2 iv at day 1 of each cycle		rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140 rituximab: rituximab 375 mg/m2 iv on days 1, 8, 15, 22, 56, 84, 112, 140
All Cause Mortality
	ARM A		ARM B		ARM C (Since April 2006)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/131 (15.3%)		25/132 (18.9%)		13/138 (9.4%)
Serious Adverse Events
	ARM A		ARM B		ARM C (Since April 2006)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/131 (3.1%)		20/132 (15.2%)		13/138 (9.4%)
Blood and lymphatic system disorders
Neutropenia	0/131 (0%)	0	3/132 (2.3%)	3	0/138 (0%)	0
Febrile neutropenia	0/131 (0%)	0	0/132 (0%)	0	1/138 (0.7%)	1
Cardiac disorders
Atrial fibrillation	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Eye disorders
Vision blurred	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Gastrointestinal disorders
Peptic ulcer	1/131 (0.8%)	1	0/132 (0%)	0	0/138 (0%)	0
Abdominal pain upper	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Vomiting	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
gastrointestinal obstruction	0/131 (0%)	0	0/132 (0%)	0	1/138 (0.7%)	1
General disorders
Death NOS	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Injection site thrombosis	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Pyrexia	0/131 (0%)	0	1/132 (0.8%)	1	2/138 (1.4%)	2
Disease prpgression NOS	1/131 (0.8%)	1	0/132 (0%)	0	0/138 (0%)	0
Immune system disorders
Allergic reactions	0/131 (0%)	0	0/132 (0%)	0	1/138 (0.7%)	1
Infections and infestations
Pneumonia	1/131 (0.8%)	1	1/132 (0.8%)	1	0/138 (0%)	0
Urosepsis	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Sepsis NOS	0/131 (0%)	0	0/132 (0%)	0	1/138 (0.7%)	1
Infection NOS	0/131 (0%)	0	0/132 (0%)	0	2/138 (1.4%)	2
Oesophageal candidiasis	0/131 (0%)	0	0/132 (0%)	0	1/138 (0.7%)	1
Injury, poisoning and procedural complications
Accident at home	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Femur fracture	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Investigations
Transaminases increased	1/131 (0.8%)	1	1/132 (0.8%)	1	0/138 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Chest wall pain	0/131 (0%)	0	0/132 (0%)	0	1/138 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pharyngeal Cancer stage unspecified	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Pancreatic carcinoma	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Acute myeloid leukemia	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Reproductive system and breast disorders
metrorrhagia	0/131 (0%)	0	0/132 (0%)	0	1/138 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/131 (0.8%)	1	0/132 (0%)	0	0/138 (0%)	0
Dyspnoea	0/131 (0%)	0	2/132 (1.5%)	2	2/138 (1.4%)	2
Bronchitis	0/131 (0%)	0	0/132 (0%)	0	1/138 (0.7%)	1
Surgical and medical procedures
Stent removal	0/131 (0%)	0	1/132 (0.8%)	1	0/138 (0%)	0
Other (Not Including Serious) Adverse Events
	ARM A		ARM B		ARM C (Since April 2006)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/131 (32.1%)		77/132 (58.3%)		59/138 (42.8%)
Gastrointestinal disorders
Nausea	7/131 (5.3%)	7	18/132 (13.6%)	18	7/138 (5.1%)	7
Abdominal pain upper	9/131 (6.9%)	9	11/132 (8.3%)	11	7/138 (5.1%)	7
General disorders
Fatigue	16/131 (12.2%)	16	13/132 (9.8%)	13	16/138 (11.6%)	16
Pyrexia	1/131 (0.8%)	1	6/132 (4.5%)	6	9/138 (6.5%)	9
Infusion related reactions	0/131 (0%)	0	21/132 (15.9%)	21	20/138 (14.5%)	20
Infections and infestations
Infection	17/131 (13%)	17	13/132 (9.8%)	13	14/138 (10.1%)	14

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.