FCR Versus FC Alone in the Treatment of Chronic Lymphocytic Leukemia (CLL) in Relapsed Patients - Full Text View

Purpose

The purpose of this study is to provide treatment for patients who have chronic lymphocytic leukemia (CLL), and to compare the use of rituximab added to fludarabine+cyclophosphamide (FC) with FC alone, to determine if rituximab lengthens the time a patient remains free of leukemia symptoms.

Condition	Intervention	Phase
Chronic Lymphocytic Leukemia	Drug: Rituximab Drug: Fludarabine Phosphate Drug: Cyclophosphamide	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:	Open-label, Multicenter, Randomized, Comparative, Phase III Study to Evaluate the Efficacy and Safety of FCR vs. FC Alone in Previously Treated Patients With CD20 Positive B-cell CLL

Resource links provided by NLM:

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine phosphate Rituximab

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Progression-free Survival (PFS) as Assessed by the Independent Review Committee (IRC) [ Time Frame: Mean observation time at time of analysis was approximately 26 months ] [ Designated as safety issue: No ]
Progression-free survival as assessed by the IRC was defined as the time between randomization and the date of first documented disease progression, relapse after response, or death from any cause, whichever came first. Patients without a PFS event were censored at their last tumor assessment date.
Number of Participants With Progression-free Survival (PFS) Events Assessed by the Independent Review Committee (IRC) [ Time Frame: Mean observation time at time of analysis was approximately 26 months ] [ Designated as safety issue: No ]
Progression-free survival as assessed by the IRC was defined as the time between randomization and the date of first documented disease progression, relapse after response, or death from any cause (PFS events), whichever came first. Patients without a PFS event were censored at their last tumor assessment date.

Secondary Outcome Measures:

Overall Survival (OS) [ Time Frame: Mean observation time at time of analysis was approximately 26 months ] [ Designated as safety issue: No ]
Overall survival was determined from the date of randomization to the date of death irrespective of cause. Patients who had not died at the time of the final analysis (clinical data cut-off) were censored at the date of the last contact.
Number of Participants With Overall Survival (OS) Events [ Time Frame: Mean observation time at time of analysis was approximately 26 months ] [ Designated as safety issue: No ]
Overall survival was determined from the date of randomization to the date of death (OS event) irrespective of cause. Patients who had not died at the time of the final analysis (clinical data cut-off) were censored at the date of the last contact.
Event-free Survival (EFS) [ Time Frame: Mean observation time at time of analysis was approximately 26 months ] [ Designated as safety issue: No ]
Event free survival was measured from the day of randomization to the date of first documented PD, relapse after response, start of a new treatment or death from any cause. Patients without an EFS event were censored at their last tumor assessment date.
Number of Participants With Event-free Survival (EFS) Events [ Time Frame: Mean observation time at time of analysis was approximately 26 months ] [ Designated as safety issue: No ]
Event free survival was measured from the day of randomization to the date of first documented Progressive Disease (PD), relapse after response, start of a new treatment or death from any cause (EFS events). Patients without an EFS event were censored at their last tumor assessment date.
Disease-free Survival (DFS) [ Time Frame: Mean observation time at time of analysis was approximately 26 months ] [ Designated as safety issue: No ]
Disease free survival was defined for all patients with a best overall response (BOR) of Complete Response (CR) and measured the time from first documented CR in a sequence of consecutive CRs until documented disease progression, relapse or death from any cause. Patients without a DFS event at the time of the analysis (clinical data cut-off) were censored at their last tumor assessment date.
Number of Participants With Disease-free Survival (DFS) Events [ Time Frame: Mean observation time at time of analysis was approximately 26 months ] [ Designated as safety issue: No ]
Disease free survival was defined for all patients with a best overall response (BOR) of Complete Response (CR) and measured the time from first documented CR in a sequence of consecutive CRs until documented disease progression, relapse or death from any cause (DFS events). Patients without a DFS event at the time of the analysis (clinical data cut-off) were censored at their last tumor assessment date.

Enrollment:	552
Study Start Date:	July 2003
Study Completion Date:	May 2012
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Fludarabine+Cyclophosphamide (FC)	Drug: Fludarabine Phosphate Intravenous repeating dose Drug: Cyclophosphamide Intravenous repeating dose
Experimental: Fludarabine+Cyclophosphamide+Rituximab (FCR)	Drug: Rituximab Intravenous repeating dose Drug: Fludarabine Phosphate Intravenous repeating dose Drug: Cyclophosphamide Intravenous repeating dose

Eligibility

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

Criteria

Inclusion Criteria:

Age ≥18 years
Established diagnosis of B-cell CLL by NCI Working Group criteria
≤1 previous line of chemotherapy
Expected survival >6 months
Acceptable hematologic status, liver function, renal function, and pulmonary function
Negative serum pregnancy test for both pre-menopausal women and for women who are < 2 years after the onset of menopause
Written informed consent

Exclusion Criteria:

Prior treatment with interferon, rituximab or other monoclonal antibody
Prior allogeneic bone marrow transplant (BMT) or autologous BMT or peripheral stem cell transplant (PBSCT) or patients who are considered to be candidates for allogeneic or autologous BMT or PSCT as assessed by their treating physician
Fertile men or women of childbearing potential not using adequate contraception
Severe Grade 3 or 4 non-hematological toxicity or prolonged (> 2 weeks) Grade 3 or 4 cytopenia on prior fludarabine or nucleoside analogue regimen
History of fludarabine-induced or clinically significant autoimmune cytopenia
History of other malignancies within 2 years prior to study entry, except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low-grade early stage localized prostate cancer treated surgically with curative intent; good prognosis ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone with curative intent.
Medical conditions requiring long term use (> 1 month) of systemic corticosteroids
Active bacterial, viral, or fungal infection requiring systemic therapy
Severe cardiac disease
Seizure disorders requiring anticonvulsant therapy
Severe chronic obstructive pulmonary disease with hypoxemia
Uncontrolled diabetes mellitus or hypertension
Transformation to aggressive B-cell malignancy.
Known infection with HIV, HCV, or hepatitis B
Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study
Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins
Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00090051

Show 87 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Biogen Idec

Genentech

More Information

Additional Information:

Clinical Study Report Synopsis This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00090051 History of Changes
Other Study ID Numbers:	102-14, BO17072
Study First Received:	August 23, 2004
Results First Received:	December 22, 2009
Last Updated:	January 14, 2013
Health Authority:	United States: Food and Drug Administration

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
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
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on June 18, 2013