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

Hoffmann-La Roche552 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

552

Conditions

Chronic Lymphocytic Leukemia

Interventions

RituximabDRUG

Intravenous repeating dose

Fludarabine PhosphateDRUG

Intravenous repeating dose

CyclophosphamideDRUG

Intravenous repeating dose

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (106)

Outcomes

Primary Outcomes

Progression-free Survival (PFS) as Assessed by the Independent Review Committee (IRC)

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.

Time frame: Mean observation time at time of analysis was approximately 26 months

Number of Participants With Progression-free Survival (PFS) Events Assessed by the Independent Review Committee (IRC)

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.

Time frame: Mean observation time at time of analysis was approximately 26 months

Final Analysis: Time to Progression-Free Survival Event

Time to progression-free survival (PFS) event was defined as the time between randomization and the date of first documented PFS event: disease progression, relapse or death by any cause, whichever came first.

Time frame: Median observation time was approximately 5 years

Secondary Outcomes

Overall Survival (OS)

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.

Time frame: Mean observation time at time of analysis was approximately 26 months

Number of Participants With Overall Survival (OS) Events

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.

Data from ClinicalTrials.gov

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Uab Comprehensive Cancer Center

Birmingham, Alabama, United States

Pacific Coast Hematology/Oncology Medical Group

Fountain Valley, California, United States

California Cancer Center Woodward Park; Community Medical Centers

Fresno, California, United States

Rush-Presbyterian St. Luke'S Medical Center

Chicago, Illinois, United States

Duke University Medical Center

Durham, North Carolina, United States

Milton S. Hershey Medical Center; Penn State Cancer Inst.

Hershey, Pennsylvania, United States

Concord Repatriation General Hospital; Haematology

Sydney, New South Wales, Australia

Mater Hospital; Division of Cancer Services

Brisbane, Queensland, Australia

Frankston Hospital; Oncology/Haematology

Frankston, Victoria, Australia

Peter Maccallum Cancer Institute; Medical Oncology

Melbourne, Victoria, Australia

...and 96 more locations

Time frame: Mean observation time at time of analysis was approximately 26 months

Event-free Survival (EFS)

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.

Time frame: Mean observation time at time of analysis was approximately 26 months

Number of Participants With Event-free Survival (EFS) Events

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.

Time frame: Mean observation time at time of analysis was approximately 26 months

Disease-free Survival (DFS)

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.

Time frame: Mean observation time at time of analysis was approximately 26 months

Number of Participants With Disease-free Survival (DFS) Events

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.

Time frame: Mean observation time at time of analysis was approximately 26 months

Final Analysis: Time to Overall Survival Event

Overall survival (OS) was determined from the date of randomization to the date of death (OS event) irrespective of cause.

Time frame: Median observation time was approximately 5 years

Final Analysis: Time to Event-Free Survival Event

Event free survival (EFS) was defined as the time from the day of randomization to the date of first EFS event: documented disease progression, relapse after response, start of a new treatment or death from any cause.

Time frame: Median observation time was approximately 5 years

Final Analysis: Percentage of Participants With Complete Response

Complete response was defined as the disappearance of all signs of cancer in response to treatment.

Time frame: Median observation time was approximately 5 years

Final Analysis: Time to Disease-Free Survival Event

Time to disease-free survival (DFS) event was defined as the time from first documented response until the first documented DFS event: disease progression, relapse or death from any cause.

Time frame: Median observation time was approximately 5 years

Final Analysis: Duration of Response

Duration of response was defined as the time between the date of the earliest qualifying response and the date of disease progression or death due to any cause.

Time frame: Median observation time was approximately 5 years

Final Analysis: Time to New Chronic Lymphocytic Leukemia (CLL) Treatment

Time to new CCL treatment was defined as the time from randomization to the first day of new treatment for CCL or death.

Time frame: Median observation time was approximately 5 years