Primary Rituximab and Maintenance

Sponsor

Lymphoma Study Association (Other)

Overall Status

Completed

CT.gov ID

NCT00140582

Collaborator

HOVON - Dutch Haemato-Oncology Association (Other), German Low Grade Lymphoma Study Group (Other), Australasian Leukaemia and Lymphoma Group (Other), Institute of Cancer Research, United Kingdom (Other)

1,217

Enrollment

Locations

Arms

144

Actual Duration (Months)

50.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Objectives
Primary objective: To evaluate in patients with advanced follicular lymphoma the benefit of maintenance therapy with rituximab after induction of response with chemotherapy plus rituximab in comparison with no maintenance therapy
Secondary objective: To evaluate response rates, event driven survival endpoints (EFS, PFS, OS) and quality of life of four different chemotherapy regimens combined with rituximab, with or without maintenance with rituximab, for first line treatment of advanced stage follicular lymphoma.
Study Design This is an international open-label, multicentre, randomized study with two treatment phases. In the induction phase patients have to respond to 1st line induction treatment in order to be eligible for randomization to the second phase of maintenance treatment or observation. After the maintenance period patients will be included in the follow up phase for 3 years.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma	Drug: Rituximab	Phase 3

Detailed Description

Study medication

First period: Induction of response with 8 x rituximab combined with 8 cycles of CVP or 6 cycles of CHOP in 21-day cycles or 6 cycles of FCM in 28-day cycles or 6 cycles of MCP in 28-day cycles.
Second period: rituximab 375 mg/m2 every 8 weeks for 24 months (12 injections) or control with no treatment

Study Design

Study Type:

Interventional

Actual Enrollment :

1217 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Advanced Follicular Lymphoma Evaluating the Benefit of Maintenance Therapy With Rituximab (MabThera®) After Induction of Response With Chemotherapy Plus Rituximab in Comparison With no Maintenance Therapy

Actual Study Start Date :

Dec 1, 2004

Actual Primary Completion Date :

May 1, 2007

Actual Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A : rituximab maintenance Maintenance with rituximab for 2 years	Drug: Rituximab rituximab 375 mg/m2 every 8 weeks for 24 months (12 injections) or control with no treatment
No Intervention: B : no maintenance No further treatment

Arm

Intervention/Treatment

Experimental: A : rituximab maintenance

Maintenance with rituximab for 2 years

Drug: Rituximab

rituximab 375 mg/m2 every 8 weeks for 24 months (12 injections) or control with no treatment

No Intervention: B : no maintenance

No further treatment

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [number of event observed driven : 344 events or 10 years]
defined as the time from randomization to progression, relapse, death from any cause.

Secondary Outcome Measures

Response rates, event driven survival endpoints (EFS, PFS, OS) [number of event observed driven : 344 events or 10 years]
Quality of life [number of event observed driven : 344 events or 10 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed follicular lymphoma grade 1, 2 or 3a.
Patients previously untreated.
Patients with at least one of the following symptoms requiring initiation of treatment:
Bulky disease at study entry according to the GELF criteria: nodal or extranodal mass > 7cm in its greater diameter
B symptoms
Elevated serum LDH or beta2-microglobulin
involvement of at least 3 nodal sites (each with a diameter greater than 3 cm)
symptomatic splenic enlargement
compressive syndrome
pleural/peritoneal effusion
Age must be > 18 years.
Performance status < 2 on the ECOG scale (see appendix E).
Adequate hematological function within 28 days prior to registration (unless those abnormalities are related to lymphoma extension), this includes:
Hemoglobin ≥ 8.0 g/dl (5.0 mmol/L)
Absolute neutrophil count (ANC) ≥ 1.5 109/L
Platelet count ≥ 100 109/L
Women are not breast feeding, are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. Men agree not to father a child during participation in the trial and during the 12 months thereafter.
Having previously signed a written informed consent form.

Exclusion Criteria:

Transformation to high-grade lymphoma (secondary to "low-grade" follicular lymphoma).
Grade 3b follicular lymphoma.
Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis).
Patients regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 20 mg/day prednisone.
Patients with prior or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer.
Major surgery (excluding lymph node biopsy) within 28 days prior to registration.
Poor renal function: Serum creatinine > 2.0 mg/dl (197 μmol/L),
Poor hepatic function: total bilirubin > 2.0 mg/dl (34 μmol/L), AST (SGOT) > 3 x the upper limit of normal unless these abnormalities are related to lymphoma.
Known HIV infection or active HBV or HCV infection.
Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease). Judgment is up to the investigator.
Life expectancy < 6 months
Known sensitivity or allergy to murine products
Treatment within a clinical trial within 30 days prior to trial entry
Adult patient under tutelage.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Fundaleu Hospital	Buenos Aires	Argentina	CP C1114AAN
2	Australian Leukemia and Lymphoma Group	Melbourne	Australia
3	Université de Gent	Gent	Belgium
4	Groupe d'Etude des Lymphomes de l'adulte	Mont-Godinne	Belgium
5	Hospital Samaritano	Sao Paulo	Brazil
6	Fundación Santafé de Bogotá	Bogota	Colombia
7	Amtssygehuset i Herlev	Herlev	Denmark
8	Polyclinique Bordeaux Nord	Bordeaux	France	33300
9	Hôpital Henri Mondor	Créteil	France	94010
10	Hématologie CHU de Lille	Lille	France	59000
11	Centre Léon Bérard	Lyon	France	69008
12	Institut Curie	Paris	France	75005
13	Hôpital Saint Louis	Paris	France	75010
14	Hématologie Adultes - Hôpital Necker	Paris	France	75743
15	Service d'Hématologie - Centre Hospitalier Lyon-Sud	Pierre-Bénite cedex	France	69495
16	Centre Hospitalier Robert Debré	Reims	France	51092
17	Centre Henri Becquerel	Rouen	France	76038
18	Hématologie CHU Purpan	Toulouse	France	31059
19	Institut Gustave Roussy	Villejuif	France
20	HOVON	Utrecht	Netherlands
21	Australia New Zealand Leukemia Lymphoma Group	Auckland	New Zealand
22	Instituo Nacional de Enfermedades Neoplasicas	Lima	Peru
23	Hospital Clinic Barcelona	Barcelona	Spain
24	King Chulalongkorn Memorial Hospital	Bangkok	Thailand