NCT00140582 · CITED IN SOURCE DOCUMENTS

Primary Rituximab and Maintenance

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2017-03-13

* 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.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Maintenance with rituximab for 2 years
intervention Names
Drug: Rituximab
label
A : rituximab maintenance
type
EXPERIMENTAL
description
No further treatment
label
B : no maintenance
type
NO_INTERVENTION

interventions

arm Group Labels
A : rituximab maintenance
description
rituximab 375 mg/m2 every 8 weeks for 24 months (12 injections) or control with no treatment
name
Rituximab
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1217
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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

secondary Outcomes

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

Full 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.
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

Source references

references

citation
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
type
DERIVED
citation
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
type
DERIVED
citation
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
type
DERIVED
citation
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
type
DERIVED