Rituximab, Cyclophosphamide, Vincristine Sulfate, and Prednisone With or Without Liposome-Encapsulated Doxorubicin Citrate in Treating Older Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Non-Hodgkin Lymphoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00911183
First received: May 29, 2009
Last updated: July 21, 2009
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: pegfilgrastim
Biological: rituximab
Drug: cyclophosphamide
Drug: liposome-encapsulated doxorubicin citrate
Drug: prednisone
Drug: vincristine sulfate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Diffuse Large B Cell Non-Hodgkin's Lymphoma in the Vulnerable/Frail Elderly. A Multicentric Randomized Phase II Trial With Emphasis on Geriatric Assessment and Quality of Life

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Complete remission rate at 6 months [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival, event-free survival, and overall survival [ Designated as safety issue: No ]
  • Overall response rate [ Designated as safety issue: No ]
  • Duration of complete remission [ Designated as safety issue: No ]
  • Acute side effects as assessed by the International CTC scale [ Designated as safety issue: Yes ]
  • Geriatric condition as assessed by the following questionnaires: the Cumulative Illness Rating Scale-Geriatric, the Mini Nutritional Assessment, the Instrumental Activities of Daily Living, the QLQ-C30, the Mini Mental State Examination, and the Geri ... [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: October 2008
Estimated Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: filgrastim
Given subcutaneously
Biological: pegfilgrastim
Given subcutaneously
Biological: rituximab
Given IV
Drug: cyclophosphamide
Given IV
Drug: prednisone
Given orally
Drug: vincristine sulfate
Given IV
Experimental: 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.
Biological: filgrastim
Given subcutaneously
Biological: pegfilgrastim
Given subcutaneously
Biological: rituximab
Given IV
Drug: cyclophosphamide
Given IV
Drug: liposome-encapsulated doxorubicin citrate
Given IV
Drug: prednisone
Given orally
Drug: vincristine sulfate
Given IV

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, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of diffuse large B-cell non-Hodgkin lymphoma

    • Stage II, III, or IV disease (according to the WHO classification), including all morphological and clinical variants

      • No Burkitt-like lymphoma (presence of small cells in the bone marrow biopsy allowed)
    • CD20+ disease
  • Has ≥ 1 measurable target lesion ≥ 1.1 cm (according to the International Workshop Criteria)
  • Poor physiological status, as defined by ≥ 1 of the following criteria:

    • WHO performance status 3
    • Clinical evaluation and measurement of LVEF that would preclude doxorubicin administration (i.e., LVEF < 50%)
    • Creatinine clearance < 50 mL/min
    • Serum bilirubin > 30 μmol/L
    • Severe comorbidity that would preclude the use of CHOP chemotherapy
  • Ineligible for standard R-CHOP therapy
  • No cerebral or meningeal involvement

PATIENT CHARACTERISTICS:

  • WHO performance status 0-3
  • ANC > 750/mm^3
  • Platelet count > 50,000/mm^3
  • LVEF > 35%
  • Able to receive either R-COP or R-COPY therapy
  • No congestive heart failure, serious arrhythmia, or myocardial infarction within the past 6 months
  • No other malignancy within the past 5 years except for adequately treated basal cell carcinoma of the skin or curatively treated carcinoma in situ of the cervix
  • No active infection
  • No active viral hepatitis B or C by serology
  • No known HIV positivity
  • No hypersensitivity to rituximab, any of its excipients, or to murine proteins
  • No documented history of allergy to eggs or egg products
  • No psychological, familial, sociological, or geographical condition that would preclude compliance with study treatment or follow-up schedule

PRIOR CONCURRENT THERAPY:

  • No prior therapy for this cancer
  • No prior anthracycline administration with a cumulative dose > 240 mg/m² of doxorubicin hydrochloride or > 400 mg/m² of epirubicin hydrochloride
  • More than 30 days since prior participation in another clinical trial involving investigational drugs
  • No other concurrent antineoplastic agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00911183

Locations
France
Institut Bergonie Recruiting
Bordeaux, France, 33076
Contact: Pierre Soubeyran, MD, PhD    33-556-333-267    soubeyran_p@bergonie.org   
Sponsors and Collaborators
Institut Bergonié
Investigators
Principal Investigator: Pierre Soubeyran, MD, PhD Institut Bergonié
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00911183     History of Changes
Other Study ID Numbers: CDR0000636032, IB-FRAIL06, INCA-RECF0892, IB-2008-25, EUDRACT-2008-001506-16
Study First Received: May 29, 2009
Last Updated: July 21, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Citric Acid
Cyclophosphamide
Rituximab
Doxorubicin
Prednisone
Vincristine
Lenograstim
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 22, 2014