FCR Versus FC Alone in the Treatment of Chronic Lymphocytic Leukemia (CLL) in Relapsed Patients
This study has been completed.
Sponsor:
Hoffmann-La Roche
Collaborators:
Biogen
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00090051
First received: August 23, 2004
Last updated: May 29, 2013
Last verified: May 2013
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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:
Genetic and Rare Diseases Information Center resources:
Chronic Lymphocytic Leukemia
Leukemia, B-cell, Chronic
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.
- Final Analysis: Time to Progression-Free Survival Event [ Time Frame: Median observation time was approximately 5 years ] [ Designated as safety issue: No ]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.
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.
- Final Analysis: Time to Overall Survival Event [ Time Frame: Median observation time was approximately 5 years ] [ Designated as safety issue: No ]Overall survival (OS) was determined from the date of randomization to the date of death (OS event) irrespective of cause.
- Final Analysis: Time to Event-Free Survival Event [ Time Frame: Median observation time was approximately 5 years ] [ Designated as safety issue: No ]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.
- Final Analysis: Percentage of Participants With Complete Response [ Time Frame: Median observation time was approximately 5 years ] [ Designated as safety issue: No ]Complete response was defined as the disappearance of all signs of cancer in response to treatment.
- Final Analysis: Time to Disease-Free Survival Event [ Time Frame: Median observation time was approximately 5 years ] [ Designated as safety issue: No ]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.
- Final Analysis: Duration of Response [ Time Frame: Median observation time was approximately 5 years ] [ Designated as safety issue: No ]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.
- Final Analysis: Time to New Chronic Lymphocytic Leukemia (CLL) Treatment [ Time Frame: Median observation time was approximately 5 years ] [ Designated as safety issue: No ]Time to new CCL treatment was defined as the time from randomization to the first day of new treatment for CCL or death.
| Enrollment: | 552 |
| Study Start Date: | July 2003 |
| Study Completion Date: | June 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 (Adult, Senior) |
| 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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00090051
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00090051
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Locations
| United States, North Carolina | |
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| Durham, North Carolina, United States | |
| Australia | |
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| Concord, Australia | |
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| East Melbourne, Australia | |
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| Frankston, Australia | |
| Belgium | |
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| Antwerpen, Belgium, 2060 | |
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| Bruxelles, Belgium | |
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| Leuven, Belgium, 3000 | |
| Canada, Alberta | |
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| Edmonton, Alberta, Canada | |
| Canada, British Columbia | |
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| Vancouver, British Columbia, Canada | |
| Canada, Newfoundland and Labrador | |
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| St Johns, Newfoundland and Labrador, Canada, A1B 3V6 | |
| Canada, Nova Scotia | |
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| Halifax, Nova Scotia, Canada | |
| Canada, Ontario | |
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| Hamilton, Ontario, Canada, L8V 5C2 | |
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| Ottawa, Ontario, Canada | |
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| Toronto, Ontario, Canada, M4N 3M5 | |
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| Toronto, Ontario, Canada | |
| Denmark | |
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| Aarhus, Denmark | |
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| Copenhagen, Denmark | |
| France | |
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| Bobigny, France | |
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| Caen Cedex, France | |
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| Clermont Ferrand Cedex 1, France | |
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| Creteil, France | |
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| Le Mans, France | |
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| Lille Cedex, France | |
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| Lyon Cedex 8, France, 69373 | |
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| Lyon, France | |
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| Marseille Cedex 9, France, 13273 | |
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| Montpellier Cedex 5, France | |
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| Nantes Cedex 1, France | |
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| Paris Cedex 04, France, 75181 | |
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| Paris Cedex 10, France, 75475 | |
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| Paris, France | |
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| Pierre Benite Cedex, France | |
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| Rouen, France | |
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| Tours, France | |
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| Vandoeuvre, France, 54500 | |
| Hungary | |
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| Budapest, Hungary, H-1122 | |
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| Budapest, Hungary, H-1135 | |
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| Debrecen, Hungary | |
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| Pecs, Hungary, H-7624 | |
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| Szeged, Hungary, H-6720 | |
| Italy | |
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| Bari, Italy | |
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| Bologna, Italy | |
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| Milano, Italy | |
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| Napoli, Italy | |
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| Pavia, Italy | |
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| Roma, Italy, 00144 | |
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| Vicenza, Italy | |
| Netherlands | |
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| Amersfoort, Netherlands, 3800 BM | |
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| Amsterdam, Netherlands | |
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| Den Haag, Netherlands, 2545 CH | |
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| Rotterdam, Netherlands | |
| New Zealand | |
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| Auckland, New Zealand | |
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| Christchurch, New Zealand | |
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| Wellington South, New Zealand | |
| Norway | |
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| Oslo, Norway | |
| Poland | |
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| Lodz, Poland | |
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| Lublin, Poland | |
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| Warszawa, Poland, 00-909 | |
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| Warszawa, Poland, 00-957 | |
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| Warszawa, Poland, 02-097 | |
| Romania | |
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| Bucharest, Romania, 022 328 | |
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| Bucharest, Romania, 030 171 | |
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| Tg. Mures, Romania, 540 136 | |
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| Timisoara, Romania, 300 079 | |
| Russian Federation | |
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| Moscow, Russian Federation, 115478 | |
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| Moscow, Russian Federation, 125167 | |
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| Moscow, Russian Federation, 129128 | |
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| Obninsk, Russian Federation, 249036 | |
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| Samara, Russian Federation, 443095 | |
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| St. Petersburg, Russian Federation, 193024 | |
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| St. Petersburg, Russian Federation, 194291 | |
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| St. Petersburg, Russian Federation, 197089 | |
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| St. Petersburg, Russian Federation, 197110 | |
| Spain | |
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| Madrid, Spain, 28006 | |
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| Madrid, Spain, 28041 | |
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| Salamanca, Spain | |
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| Zaragoza, Spain | |
| Sweden | |
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| Linkoping, Sweden | |
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| Stockholm, Sweden | |
| United Kingdom | |
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| Bournemouth, United Kingdom | |
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| Cambridge, United Kingdom | |
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| Glasgow, United Kingdom | |
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| Leeds, United Kingdom | |
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| Liverpool, United Kingdom | |
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| London, United Kingdom, EC1A 7BE | |
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| London, United Kingdom, SW3 6JJ | |
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| Wakefield, United Kingdom | |
Sponsors and Collaborators
Hoffmann-La Roche
Biogen
Genentech, Inc.
More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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: | May 29, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Leukemia, Lymphocytic, Chronic, B-Cell Rituximab Leukemia Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Leukemia, B-Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cyclophosphamide Fludarabine phosphate |
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 Antimetabolites, Antineoplastic Antimetabolites |
ClinicalTrials.gov processed this record on September 27, 2016