Primary Rituximab and Maintenance

Follicular Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00140582
• Other study ID #: PRIMA
• Status: Completed
• Phase: Phase 3
• First received: August 22, 2005
• Last updated: March 9, 2017
• Start date: December 2004
• Est. completion date: December 2016

Study information

• Verified date: March 2017
• Source: Lymphoma Study Association
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1217
• Est. completion date: December 2016
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

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

Locations

Country	Name	City	State
Argentina	Fundaleu Hospital	Buenos Aires
Australia	Australian Leukemia and Lymphoma Group	Melbourne
Belgium	Université de Gent	Gent
Belgium	Groupe d'Etude des Lymphomes de l'adulte	Mont-Godinne
Brazil	Hospital Samaritano	Sao Paulo
Colombia	Fundación Santafé de Bogotá	Bogota
Denmark	Amtssygehuset i Herlev	Herlev
France	Polyclinique Bordeaux Nord	Bordeaux
France	Hôpital Henri Mondor	Créteil
France	Hématologie CHU de Lille	Lille
France	Centre Léon Bérard	Lyon
France	Hématologie Adultes - Hôpital Necker	Paris
France	Hôpital Saint Louis	Paris
France	Institut Curie	Paris
France	Service d'Hématologie - Centre Hospitalier Lyon-Sud	Pierre-Bénite cedex
France	Centre Hospitalier Robert Debré	Reims
France	Centre Henri Becquerel	Rouen
France	Hématologie CHU Purpan	Toulouse
France	Institut Gustave Roussy	Villejuif
Netherlands	HOVON	Utrecht
New Zealand	Australia New Zealand Leukemia Lymphoma Group	Auckland
Peru	Instituo Nacional de Enfermedades Neoplasicas	Lima
Spain	Hospital Clinic Barcelona	Barcelona
Thailand	King Chulalongkorn Memorial Hospital	Bangkok

Sponsors (5)

Lead Sponsor	Collaborator
Lymphoma Study Association	Australasian Leukaemia and Lymphoma Group, German Low Grade Lymphoma Study Group (GLSG/OSHO), HOVON - Dutch Haemato-Oncology Association, Institute of Cancer Research, United Kingdom

Countries where clinical trial is conducted

Argentina,  Australia,  Belgium,  Brazil,  Colombia,  Denmark,  France,  Netherlands,  New Zealand,  Peru,  Spain,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	defined as the time from randomization to progression, relapse, death from any cause.	number of event observed driven : 344 events or 10 years
Secondary	Response rates, event driven survival endpoints (EFS, PFS, OS)		number of event observed driven : 344 events or 10 years
Secondary	Quality of life		number of event observed driven : 344 events or 10 years

External Links

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