Primary Rituximab and Maintenance

NCT00140582 | Completed Phase 3 DMC

• 1 other identifier: PRIMA
• Study Type: interventional
• Target: 1,217
• Locations: 12 countries
• Sites: 24

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.

Conditions

Follicular Lymphoma

Keywords

lymphoma; follicular; maintenance

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (2)

A : rituximab maintenance

EXPERIMENTAL

Maintenance with rituximab for 2 years

Drug: Rituximab

B : no maintenance

NO INTERVENTION

No further treatment

Interventions

Rituximab DRUG

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

A : rituximab maintenance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lymphoma Study Association: lead
• HOVON - Dutch Haemato-Oncology Association: collaborator
• German Low Grade Lymphoma Study Group: collaborator
• Australasian Leukaemia and Lymphoma Group: collaborator
• Institute of Cancer Research, United Kingdom: collaborator

Study Sites (24)

Fundaleu Hospital

Buenos Aires, CP C1114AAN, Argentina

Location

Australian Leukemia and Lymphoma Group

Melbourne, Australia

Location

Université de Gent

Ghent, Belgium

Location

Groupe d'Etude des Lymphomes de l'adulte

Mont-Godinne, Belgium

Location

Hospital Samaritano

São Paulo, Brazil

Location

Fundación Santafé de Bogotá

Bogotá, Colombia

Location

Amtssygehuset i Herlev

Herlev, Denmark

Location

Polyclinique Bordeaux Nord

Bordeaux, 33300, France

Location

Hôpital Henri Mondor

Créteil, 94010, France

Location

Hématologie CHU de Lille

Lille, 59000, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut Curie

Paris, 75005, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Hématologie Adultes - Hôpital Necker

Paris, 75743, France

Location

Service d'Hématologie - Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier Robert Debré

Reims, 51092, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Hématologie CHU Purpan

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, France

Location

HOVON

Utrecht, Netherlands

Location

Australia New Zealand Leukemia Lymphoma Group

Auckland, New Zealand

Location

Instituo Nacional de Enfermedades Neoplasicas

Lima, Peru

Location

Hospital Clinic Barcelona

Barcelona, Spain

Location

King Chulalongkorn Memorial Hospital

Bangkok, Thailand

Location

Related Publications (4)

• Bachy E, Seymour JF, Feugier P, Offner F, Lopez-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. doi: 10.1200/JCO.19.01073. Epub 2019 Jul 24.

  PMID: 31339826 DERIVED

• Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. doi: 10.1179/1607845414Y.0000000179. Epub 2014 Jul 16.

  PMID: 25029908 DERIVED

• Ghesquieres H, Cartron G, Seymour JF, Delfau-Larue MH, Offner F, Soubeyran P, Perrot A, Brice P, Bouabdallah R, Sonet A, Dupuis J, Casasnovas O, Catalano JV, Delmer A, Jardin F, Verney A, Dartigues P, Salles G. Clinical outcome of patients with follicular lymphoma receiving chemoimmunotherapy in the PRIMA study is not affected by FCGR3A and FCGR2A polymorphisms. Blood. 2012 Sep 27;120(13):2650-7. doi: 10.1182/blood-2012-05-431825. Epub 2012 Aug 10.

  PMID: 22885164 DERIVED

• Salles G, Seymour JF, Offner F, Lopez-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Ferme C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. doi: 10.1016/S0140-6736(10)62175-7. Epub 2010 Dec 20.

  PMID: 21176949 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Gilles A Salles, MD PhD

  Lymphoma Study Association

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2005
• First Posted: September 1, 2005
• Study Start: December 1, 2004
• Primary Completion: May 1, 2007
• Study Completion: December 1, 2016
• Last Updated: March 13, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); BR (1); AR (1); NZ (1); PE (1); ES (1); TH (1); AU (1); BE (2); CO (1); FR (12); NL (1)