FCR or BR in Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia - Full Text View

Sponsor:	German CLL Study Group
Collaborators:	Roche Pharma AG Mundipharma
Information provided by (Responsible Party):	German CLL Study Group
ClinicalTrials.gov Identifier:	NCT00769522

Purpose

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	Intervention	Phase
Leukemia	Biological: rituximab Drug: bendamustine hydrochloride Drug: cyclophosphamide Drug: fludarabine phosphate	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Acute Lymphocytic Leukemia Cancer Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Cyclophosphamide Bendamustine hydrochloride Bendamustine Fludarabine Fludarabine phosphate Rituximab

U.S. FDA Resources

Further study details as provided by German CLL Study Group:

Primary Outcome Measures:

Progression-free survival rate after 24 months [ Time Frame: 2008-2015 ] [ Designated as safety issue: No ]
estimated time point when 198 needed events for the final analysis(PD or deaths) have occured.

Secondary Outcome Measures:

Minimal residual disease, complete response rates, and partial response rates [ Time Frame: 2008-2015 ] [ Designated as safety issue: No ]
done within the final analysis
Duration of remission [ Time Frame: 2008-2015 ] [ Designated as safety issue: No ]
done within the final analysis
Event-free survival [ Time Frame: 2008-2015 ] [ Designated as safety issue: No ]
done within the final analysis
Overall survival [ Time Frame: 2008-2015 ] [ Designated as safety issue: No ]
done within the final analysis
Overall response rate [ Time Frame: 2008-2015 ] [ Designated as safety issue: No ]
done within the final analysis
Response rates in and survival times in biological subgroups [ Time Frame: 2008-2015 ] [ Designated as safety issue: No ]
done within the final analysis
Toxicity rates [ Time Frame: 2008-2015 ] [ Designated as safety issue: Yes ]
done within the final analysis
Quality of life [ Time Frame: 2008-2015 ] [ Designated as safety issue: No ]
done within the final analysis
Standard safety analysis [ Time Frame: 2008-2015 ] [ Designated as safety issue: Yes ]
done within the final analysis

Enrollment:	564
Study Start Date:	September 2008
Estimated Study Completion Date:	January 2018
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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.	Biological: rituximab Given IV Other Name: Mabthera Drug: cyclophosphamide Given IV Other Name: Endoxan Drug: fludarabine phosphate Given IV Other Name: Fludarabine
Experimental: 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.	Biological: rituximab Given IV Other Name: Mabthera Drug: bendamustine hydrochloride Given IV Other Names: Levact Ribomustin Treanda

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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:
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
- 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:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00769522

Locations

Germany
Medizinische Universitaetsklinik I at the University of Cologne
Cologne, Germany, D-50924

Sponsors and Collaborators

German CLL Study Group

Roche Pharma AG

Mundipharma

Investigators

Principal Investigator:

Barbara Eichhorst, MD

Medizinische Universitaetsklinik I at the University of Cologne

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	German CLL Study Group
ClinicalTrials.gov Identifier:	NCT00769522 History of Changes
Other Study ID Numbers:	CDR0000616169, GCLLSG-CLL10, 2007-007587-21
Study First Received:	October 8, 2008
Last Updated:	March 14, 2012
Health Authority:	Germany: Paul-Ehrlich Institute

Keywords provided by German CLL Study Group:

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

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine monophosphate
Rituximab
Nitrogen Mustard Compounds
Bendamustine

Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on May 23, 2012