Fludarabine, Cyclophosphamide, and Rituximab or Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia - Full Text View

Sponsored by:	Groupe Ouest Est d'etude des Leucemies et Autres Maladies du Sang
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00564512

Purpose

RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to kill cancer cells or stop them from growing. Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. It is not yet known whether giving fludarabine and cyclophosphamide together with rituximab is more effective than giving fludarabine and cyclophosphamide together with alemtuzumab in treating B-cell chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying giving fludarabine together with cyclophosphamide and rituximab to see how well it works as first-line therapy compared with giving fludarabine together with cyclophosphamide and alemtuzumab in treating patients with B-cell chronic lymphocytic leukemia.

Condition	Intervention	Phase
Leukemia	Drug: alemtuzumab Drug: cyclophosphamide Drug: fludarabine phosphate Drug: rituximab	Phase III

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Rituximab Alemtuzumab Campath

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
Official Title:	Phase III, Multicenter, European, Randomized Trial Comparing the Combination Fludarabine Phosphate-Cyclophosphamide-Rituximab (FCR) With the Combination Fludarabine Phosphate-Cyclophosphamide-Campath (FCCam) in Previously Untreated Adults With B and C Binet Stage B-Chronic Lymphoid Leukemia (B-CLL)

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

Primary Outcome Measures:

Progression-free survival at 36 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Disease-free survival [ Designated as safety issue: No ]
Event-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Time to next treatment [ Designated as safety issue: No ]
Overall response rate (complete response [CR] and partial response [PR]) [ Designated as safety issue: No ]
Duration of phenotypic, molecular, NCI complete and partial responses [ Designated as safety issue: No ]
Response rates and survival times in biological subgroups [ Designated as safety issue: No ]
Treatment-related adverse effects [ Designated as safety issue: Yes ]
Quality of life [ Designated as safety issue: No ]

Estimated Enrollment:	310
Study Start Date:	November 2007

Detailed Description:

OBJECTIVES:

Primary

To compare 36-month progression-free survival in patients with Binet stage B or C B-cell chronic lymphocytic leukemia treated with first-line therapy comprising fludarabine phosphate and cyclophosphamide and either rituximab or alemtuzumab.

Secondary

To compare the disease-free survival, event-free survival, and overall survival of patients treated with these regimens.
To compare time to next treatment in patients treated with these regimens.
To compare the overall response rate (complete response [CR] and partial response [PR]) in patients treated with these regimens.
To compare the rate of phenotypic and molecular response in patients treated with these regimens.
To compare the duration of phenotypic, molecular, complete and partial responses in patients treated with these regimens.
To compare the response rates and survival times in biological subgroups.
To compare the rates of treatment-related adverse effects in patients treated with these regimens.
To compare the quality of life of patients treated with these regimens.
Minimal residual disease study.

OUTLINE: This is a multicenter study. Patients are stratified according to Ig mutational status and cytogenetic abnormalities. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive rituximab IV on day 1 and fludarabine phosphate and cyclophosphamide IV or orally on days 2-4 of course 1. Beginning in course 2 and for all subsequent courses, patients receive rituximab IV on day 1 and fludarabine phosphate and cyclophosphamide IV or orally on days 1-3.
Arm II: Patients receive alemtuzumab subcutaneously, oral fludarabine phosphate, and oral cyclophosphamide on days 1-3.

In both arms, treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Inclusion

Diagnosis of B-cell chronic lymphocytic leukemia (CLL), meeting the following criteria:
- Binet classification stages B or C
- Del 17 p (FISH) negative (< 10 % positives cores)
- Matutes score 4 or 5

Exclusion

Transformation to aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma, or prolymphocytic leukemia)

PATIENT CHARACTERISTICS:

Exclusion

ECOG performance status ≥ 2
Life expectancy < 6 months
Creatinine clearance < 60 mL/min
Total bilirubin > 2 x upper limit of normal (ULN)
Gamma glutamyltransferase or transaminase levels > 2 x ULN
Cumulative illness rating scale > 6
HIV seropositivity
Hepatitis B or C seropositivity (unless clearly due to vaccination)
Clinically significant autoimmune anemia
Active bacterial, viral, or fungal infection
Active second malignancy currently requiring treatment (except basal cell carcinoma or in situ endometrial carcinoma) and/or less than 5 years complete remission after breast cancer
Any severe comorbid conditions including, but not limited to, any of the following:
- Class III or IV heart failure
- Recent myocardial infarction
- Unstable angina
- Ventricular tachyarrhythmias requiring ongoing treatment
- Severe chronic obstructive pulmonary disease with hypoxemia
- Uncontrolled diabetes mellitus
- Uncontrolled hypertension
Concomitant disease requiring prolonged use of corticosteroids (> 1 month)
Known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs
Contraindication to the use of rituximab or alemtuzumab according to Summary of Product Characteristics
Any coexisting medical or psychological condition that would preclude participation in the required study procedures
Any mental deficiency preventing proper understanding of the requirements of treatment
Person under law control
Pregnant or breastfeeding women
Fertile patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study

PRIOR CONCURRENT THERAPY:

Inclusion

No prior chemotherapy, radiotherapy, or immunotherapy for CLL
Corticosteroids within the past month allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00564512

Locations

France
Centre Henri Becquerel	Recruiting
Rouen, France, 76038
Contact: Stephane Lepretre, MD 33-2-3208-2223

Sponsors and Collaborators

Groupe Ouest Est d'etude des Leucemies et Autres Maladies du Sang

Investigators

Study Chair:	Stephane Lepretre, MD	Centre Henri Becquerel
Investigator:	Pierre Feugier	CHU de Nancy - Hopitaux de Brabois

More Information

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

Study ID Numbers:	CDR0000577580, CLL-2007-FMP, INCA-RECF0496, EudraCT-2007-000327-18
Study First Received:	November 27, 2007
Last Updated:	December 31, 2008
ClinicalTrials.gov Identifier:	NCT00564512
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

B-cell chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Vidarabine
Leukemia, Lymphoid
Immunoproliferative Disorders
Rituximab
Leukemia, B-cell, chronic
Cyclophosphamide
Fludarabine monophosphate

Leukemia
Lymphatic Diseases
Leukemia, Lymphocytic, Chronic, B-Cell
Alemtuzumab
Fludarabine
Leukemia, B-Cell
Lymphoproliferative Disorders

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs

Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 15, 2009