Diffuse Large B Cell Non-Hodgkin's Lymphoma in the Vulnerable/Frail Elderly. A Multicentric Randomized Phase II Trial

Phase 2

Completed

Conditions: Lymphoma

Interventions: Biological: filgrastim
Biological: pegfilgrastim
Biological: rituximab
Drug: cyclophosphamide
Drug: prednisone
Drug: liposome-encapsulated doxorubicin citrate
Drug: vincristine sulfate

Registration Number: NCT00911183

Lead Sponsor: Institut Bergonié

Brief Summary: RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, prednisone, and liposome-encapsulated doxorubicin citrate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether rituximab and combination chemotherapy are more effective when given together with or without liposome-encapsulated doxorubicin citrate in treating older patients with diffuse large B-cell non-Hodgkin lymphoma.

PURPOSE: This randomized phase II trial is studying the side effects of giving rituximab together with cyclophosphamide, vincristine sulfate, and prednisone with or without liposome-encapsulated doxorubicin citrate and to see how well it works in treating older patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin lymphoma.

Detailed Description: OBJECTIVES:

Primary

* To assess the therapeutic efficacy of rituximab, cyclophosphamide, vincristine sulfate, and prednisone with vs without liposome-encapsulated doxorubicin citrate, in terms of complete remission rate at 6 months, in vulnerable or frail elderly patients with stage II, III, or IV diffuse large B-cell non-Hodgkin lymphoma.

* To assess the safety of these regimens in these patients.

Secondary

* To evaluate the progression-free survival, event-free survival, and overall survival rates at 6 and 24 months in patients treated with these regimens.

* To evaluate the overall response rate at 6 and 24 months in patients treated with these regimens.

* To evaluate the duration of complete remission in patients treated with these regimens.

* To evaluate the acute side effects (according to the International CTC scale) of these regimens in these patients.

* To evaluate the geriatric condition and quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

* Arm I (R-COP regimen): Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.

* Arm II (R-COPY regimen): Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.

After 3 courses of R-COP or R-COPY, patients undergo evaluation. Patients with disease progression or a response of \< 25% are removed from the study. Patients with a response of ≥ 25% receive 3 more courses of R-COP or R-COPY, followed by rituximab IV alone on day 1 of courses 7 and 8 in the absence of disease progression or unacceptable toxicity.

After the completion of chemotherapy, some patients may undergo radiotherapy.

Patients complete quality of life and geriatric assessment questionnaires at baseline and periodically during study treatment.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 67

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (R-COP regimen)	filgrastim	Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.
Arm I (R-COP regimen)	pegfilgrastim	Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.
Arm I (R-COP regimen)	rituximab	Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.
Arm I (R-COP regimen)	prednisone	Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.
Arm II (R-COPY regimen)	filgrastim	Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.
Arm II (R-COPY regimen)	pegfilgrastim	Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.
Arm II (R-COPY regimen)	rituximab	Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.
Arm II (R-COPY regimen)	cyclophosphamide	Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.
Arm II (R-COPY regimen)	liposome-encapsulated doxorubicin citrate	Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.
Arm II (R-COPY regimen)	prednisone	Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.
Arm II (R-COPY regimen)	vincristine sulfate	Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.
Arm I (R-COP regimen)	vincristine sulfate	Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.
Arm I (R-COP regimen)	cyclophosphamide	Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.

Primary Outcome Measures

Name	Time	Method
Number of Participants in Complete Remission 6 Months After Randomization	6 months after randomization	Complete remission \[CR\] is defined according to Cheson criteria. CR requires the following: 1. Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities. 2. All lymph nodes and nodal masses must have regressed to normal size. Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have decreased to ≤1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). 3. The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. 4. If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site.
Number of Participants With Severe Toxicity	6 months after randomization	Severe toxicity, defined as febrile neutropenia or toxic death. Febrile neutropenia is defined in the International CTC toxicity scale as "fever of unknown origin without clinically or microbiologically documented infection: neutrophils \< 1.0 x 109/l and fever ≥ 38.5° C. Toxic death is defined as any death which occur during treatment (from day 1 of the first cycle of chemotherapy up to day 30 of the last cycle) and is not related to lymphoma.

Secondary Outcome Measures

Name	Time	Method
Overall Survival Time	from randomization, up to 5 years	OS is defined as the delay between the date of randomization and the date of death
Progression-free Survival Time	from randomization, up to 5 years	Delay between the date of randomization and the date of progression or death. Progression is defined according to the Cheson criteria.