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

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
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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Locations


United States, North Carolina
Research Site
Durham, North Carolina, United States
Australia
Research Site
Concord, Australia
Research Site
East Melbourne, Australia
Research Site
Frankston, Australia
Belgium
Research Site
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
Research Site
Vancouver, British Columbia, Canada
Canada, Newfoundland and Labrador
Research Site
St Johns, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Nova Scotia
Research Site
Halifax, Nova Scotia, Canada
Canada, Ontario
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Hamilton, Ontario, Canada, L8V 5C2
Research Site
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, France
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Lyon Cedex 8, France, 69373
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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, France
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Paris Cedex 04, France, 75181
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Paris Cedex 10, France, 75475
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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
Research Site
Warszawa, Poland, 02-097
Research Site
Warszawa, Poland, 00-909
Research Site
Warszawa, Poland, 00-957
Romania
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Bucharest, Romania, 022 328
Research Site
Bucharest, Romania, 030 171
Research Site
Tg. Mures, Romania, 540 136
Research Site
Timisoara, Romania, 300 079
Russian Federation
Research Site
Moscow, Russian Federation, 125167
Research Site
Moscow, Russian Federation, 115478
Research Site
Moscow, Russian Federation, 129128
Research Site
Obninsk, Russian Federation, 249036
Research Site
Samara, Russian Federation, 443095
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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
Research Site
St. Petersburg, Russian Federation, 193024
Spain
Research Site
Madrid, Spain, 28041
Research Site
Madrid, Spain, 28006
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Salamanca, Spain
Research Site
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
Research Site
Glasgow, United Kingdom
Research Site
Leeds, United Kingdom
Research Site
Liverpool, United Kingdom
Research Site
London, United Kingdom, SW3 6JJ
Research Site
London, United Kingdom, EC1A 7BE
Research Site
Wakefield, United Kingdom

Sponsors and Collaborators

Hoffmann-La Roche

Biogen Idec

Genentech, Inc.

More Information

Additional Information:

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

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Weisser M, Yeh RF, Duchateau-Nguyen G, Palermo G, Nguyen TQ, Shi X, Stinson SY, Yu N, Dufour A, Robak T, Salogub GN, Dmoszynska A, Solal-Celigny P, Warzocha K, Loscertales J, Catalano J, Larratt L, Rossiev VA, Bence-Bruckler I, Geisler CH, Montillo M, Fischer K, Fink AM, Hallek M, Bloehdorn J, Busch R, Benner A, Döhner H, Valente N, Wenger MK, Stilgenbauer S, Dornan D. PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia. Blood. 2014 Jul 17;124(3):420-5. doi: 10.1182/blood-2013-12-538975. Epub 2014 Jun 10.

Dufour A, Palermo G, Zellmeier E, Mellert G, Duchateau-Nguyen G, Schneider S, Benthaus T, Kakadia PM, Spiekermann K, Hiddemann W, Braess J, Truong S, Patten N, Wu L, Lohmann S, Dornan D, GuhaThakurta D, Yeh RF, Salogub G, Solal-Celigny P, Dmoszynska A, Robak T, Montillo M, Catalano J, Geisler CH, Weisser M, Bohlander SK. Inactivation of TP53 correlates with disease progression and low miR-34a expression in previously treated chronic lymphocytic leukemia patients. Blood. 2013 May 2;121(18):3650-7. doi: 10.1182/blood-2012-10-458695. Epub 2013 Mar 22.


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 Leukemia, Lymphoid Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Cyclophosphamide Fludarabine Fludarabine phosphate	Alkylating Agents Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents Antineoplastic Agents, Alkylating Antirheumatic Agents Immunologic Factors Immunosuppressive Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Pharmacologic Actions Physiological Effects of Drugs Therapeutic Uses

ClinicalTrials.gov processed this record on March 01, 2015