FCR or BR in Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia
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| ClinicalTrials.gov Identifier: NCT00769522 |
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Recruitment Status :
Completed
First Posted : October 9, 2008
Last Update Posted : August 6, 2019
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RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. It is not yet known whether giving fludarabine and cyclophosphamide together with rituximab is more effective than giving bendamustine together with rituximab in treating chronic lymphocytic leukemia.
PURPOSE: This randomized phase III trial is studying fludarabine, cyclophosphamide, and rituximab to see how well they work compared with bendamustine and rituximab in treating patients with previously untreated B-cell chronic lymphocytic leukemia.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Lymphocytic Leukemia | Biological: Rituximab Drug: Bendamustine Drug: Cyclophosphamide Drug: Fludarabine | Phase 3 |
OBJECTIVES:
- To compare the therapeutic efficacy of fludarabine phosphate, cyclophosphamide, and rituximab vs bendamustine hydrochloride and rituximab in patients with previously untreated B-cell chronic lymphocytic leukemia.
- To compare the incidence of major side effects (e.g., myelosuppression) associated with these regimens in these patients.
- To compare the rate of infections and secondary neoplasias in patients treated with these regimens.
OUTLINE: This is a multicenter study. Patients are stratified according to country and disease stage. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive fludarabine phosphate IV and cyclophosphamide IV on days 1-3. Patients also receive rituximab IV on day 0 of course 1 and on day 1 of courses 2-6. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive bendamustine hydrochloride IV on days 1 and 2. Patients also receive rituximab as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients complete quality of life questionnaires (EORTC-C30 and EURO-QOL) at baseline and then at 12, 24, 36, 48, and 60 months.
After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year thereafter.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 564 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase III Trial of Combined Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab (FCR) Versus Bendamustine and Rituximab (BR) in Patients With Previously Untreated Chronic Lymphocytic Leukaemia |
| Actual Study Start Date : | October 2, 2008 |
| Actual Primary Completion Date : | July 2011 |
| Actual Study Completion Date : | January 2018 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: FCR |
Biological: Rituximab
cycle 1: 375 mg/m² i.v., day 0, q28d cycle 2-6: 500 mg/m² i.v., day 1, q28d Other Names:
Drug: Cyclophosphamide cycle 1-6: 250 mg/m² i.v., days 1-3, q28d
Other Name: Endoxan Drug: Fludarabine cycle 1-6: 25 mg/m² i.v., days 1-3, q28d
Other Name: Fludura |
| Experimental: BR |
Biological: Rituximab
cycle 1: 375 mg/m² i.v., day 0, q28d cycle 2-6: 500 mg/m² i.v., day 1, q28d Other Names:
Drug: Bendamustine cycle 1-6: 90mg/m² i.v., day 1-2, q28d
Other Names:
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- Progression-free survival rate after 24 months [ Time Frame: 2008-2015 ]estimated time point when 198 needed events for the final analysis(PD or deaths) have occured.
- Minimal residual disease, complete response rates, and partial response rates [ Time Frame: 2008-2015 ]done within the final analysis
- Duration of remission [ Time Frame: 2008-2015 ]done within the final analysis
- Event-free survival [ Time Frame: 2008-2015 ]done within the final analysis
- Overall survival [ Time Frame: 2008-2015 ]done within the final analysis
- Overall response rate [ Time Frame: 2008-2015 ]done within the final analysis
- Response rates in and survival times in biological subgroups [ Time Frame: 2008-2015 ]done within the final analysis
- Toxicity rates [ Time Frame: 2008-2015 ]done within the final analysis
- Quality of life [ Time Frame: 2008-2015 ]done within the final analysis
- Standard safety analysis [ Time Frame: 2008-2015 ]done within the final analysis
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
- Confirmed diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria:
- Binet stage C disease or stage B or A disease requiring treatment
- Binet stage B or A disease meeting ≥ 1 of the following:
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B-symptoms (e.g., night sweats, weight loss ≥ 10% within the past 6 months, fevers > 38°C or 100.4°F for ≥ 2 weeks without evidence of infection) or constitutional symptoms (e.g., fatigue)
- Progressive lymphocytosis, defined as peripheral lymphocyte count > 5 x 10^9/L (i.e., > 50% increase over a 2-month period or doubling of peripheral blood lymphocyte count < 6 months)
- Evidence of progressive marrow failure as manifested by the development/worsening of anemia and/or thrombocytopenia
- Massive, progressive, or painful splenomegaly or hypersplenism
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Massive lymph nodes or lymph node clusters (> 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
- No 17p deletion by FISH
- No aggressive B-cell cancer, such as Richter syndrome
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Life expectancy ≥ 6 months
- Total bilirubin ≤ 2 times upper limit of normal (ULN) (unless directly attributable to CLL)
- AST and ALT ≤ 2 times ULN (unless directly attributable to CLL)
- Creatinine clearance ≥ 70 mL/min (creatinine clearance is to be calculated only in patients with serum creatinine ≥ 1.1 mg/dL)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
- Hepatitis B and C negative
- HIV negative
- CIRS score > 6 or a single score of 4 for one organ category
- No active secondary malignancy requiring treatment, except basal cell carcinoma or malignant tumor curatively treated by surgery, or successfully treated secondary malignancies in complete remission > 5 years prior to enrollment
- No history of anaphylaxis following exposure to monoclonal antibodies
- No active bacterial, viral, or fungal infection
- No medical condition requiring prolonged use of oral corticosteroids (i.e., > 1 month)
- No cerebral dysfunction or legal incapacity
- No circumstance that would preclude completion of the study or the required follow-up
PRIOR CONCURRENT THERAPY:
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No prior CLL specific-chemotherapy, radiotherapy, and/or immunotherapy
- Prednisolone administered immediately prior to initiation of study therapy allowed for very high lymphocyte counts
- No concurrent participation in another clinical trial
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00769522
| Germany | |
| Medizinische Universitaetsklinik I at the University of Cologne | |
| Cologne, Germany, D-50924 | |
| Principal Investigator: | Barbara Eichhorst, MD | Medizinische Universitaetsklinik I at the University of Cologne |
Publications of Results:
Other Publications:
| Responsible Party: | German CLL Study Group |
| ClinicalTrials.gov Identifier: | NCT00769522 |
| Other Study ID Numbers: |
CLL10 CDR0000616169 ( Other Identifier: Clinical Data Repository ) 2007-007587-21 ( EudraCT Number ) |
| First Posted: | October 9, 2008 Key Record Dates |
| Last Update Posted: | August 6, 2019 |
| Last Verified: | August 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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B-cell chronic lymphocytic leukemia stage 0 chronic lymphocytic leukemia stage I chronic lymphocytic leukemia |
stage II chronic lymphocytic leukemia stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia |
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Leukemia Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Neoplasms by Histologic Type Neoplasms Hematologic Diseases Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Leukemia, B-Cell Chronic Disease Disease Attributes Pathologic Processes |
Cyclophosphamide Bendamustine Hydrochloride Rituximab Fludarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Immunological |