MedPath

Primary Rituximab and Maintenance

Phase 3
Completed
Conditions
Follicular Lymphoma
Interventions
Registration Number
NCT00140582
Lead Sponsor
Lymphoma Study Association
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.

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1217
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
A : rituximab maintenanceRituximabMaintenance with rituximab for 2 years
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Quality of lifenumber of event observed driven : 344 events or 10 years
Response rates, event driven survival endpoints (EFS, PFS, OS)number of event observed driven : 344 events or 10 years

Trial Locations

Locations (24)

Hôpital Henri Mondor

🇫🇷

Créteil, France

Hématologie CHU Purpan

🇫🇷

Toulouse, France

Université de Gent

🇧🇪

Gent, Belgium

Amtssygehuset i Herlev

🇩🇰

Herlev, Denmark

Hospital Samaritano

🇧🇷

Sao Paulo, Brazil

Hématologie Adultes - Hôpital Necker

🇫🇷

Paris, France

Groupe d'Etude des Lymphomes de l'adulte

🇧🇪

Mont-Godinne, Belgium

Hématologie CHU de Lille

🇫🇷

Lille, France

Centre Léon Bérard

🇫🇷

Lyon, France

Hospital Clinic Barcelona

🇪🇸

Barcelona, Spain

Centre Henri Becquerel

🇫🇷

Rouen, France

Australian Leukemia and Lymphoma Group

🇦🇺

Melbourne, Australia

Fundación Santafé de Bogotá

🇨🇴

Bogota, Colombia

Polyclinique Bordeaux Nord

🇫🇷

Bordeaux, France

Service d'Hématologie - Centre Hospitalier Lyon-Sud

🇫🇷

Pierre-Bénite cedex, France

Hôpital Saint Louis

🇫🇷

Paris, France

Australia New Zealand Leukemia Lymphoma Group

🇳🇿

Auckland, New Zealand

Fundaleu Hospital

🇦🇷

Buenos Aires, Argentina

Institut Curie

🇫🇷

Paris, France

Centre Hospitalier Robert Debré

🇫🇷

Reims, France

HOVON

🇳🇱

Utrecht, Netherlands

King Chulalongkorn Memorial Hospital

🇹🇭

Bangkok, Thailand

Instituo Nacional de Enfermedades Neoplasicas

🇵🇪

Lima, Peru

Institut Gustave Roussy

🇫🇷

Villejuif, France

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