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

This study has been completed.
Sponsor:
Collaborators:
Biogen Idec
Genentech
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
  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:


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

  Hide Study Locations
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
Research Site
Bruxelles, Belgium
Research Site
Leuven, Belgium, 3000
Canada, Alberta
Research Site
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
Research Site
Hamilton, Ontario, Canada, L8V 5C2
Research Site
Ottawa, Ontario, Canada
Research Site
Toronto, Ontario, Canada
Research Site
Toronto, Ontario, Canada, M4N 3M5
Denmark
Research Site
Aarhus, Denmark
Research Site
Copenhagen, Denmark
France
Research Site
Bobigny, France
Research Site
Caen Cedex, France
Research Site
Clermont Ferrand Cedex 1, France
Research Site
Creteil, France
Research Site
Le Mans, France
Research Site
Lille Cedex, France
Research Site
Lyon, France
Research Site
Lyon Cedex 8, France, 69373
Research Site
Marseille Cedex 9, France, 13273
Research Site
Montpellier Cedex 5, France
Research Site
Nantes Cedex 1, France
Research Site
Paris, France
Research Site
Paris Cedex 04, France, 75181
Research Site
Paris Cedex 10, France, 75475
Research Site
Pierre Benite Cedex, France
Research Site
Rouen, France
Research Site
Tours, France
Research Site
Vandoeuvre, France, 54500
Hungary
Research Site
Budapest, Hungary, H-1122
Research Site
Budapest, Hungary, H-1135
Research Site
Debrecen, Hungary
Research Site
Pecs, Hungary, H-7624
Research Site
Szeged, Hungary, H-6720
Italy
Research Site
Bari, Italy
Research Site
Bologna, Italy
Research Site
Milano, Italy
Research Site
Napoli, Italy
Research Site
Pavia, Italy
Research Site
Roma, Italy, 00144
Research Site
Vicenza, Italy
Netherlands
Research Site
Amersfoort, Netherlands, 3800 BM
Research Site
Amsterdam, Netherlands
Research Site
Den Haag, Netherlands, 2545 CH
Research Site
Rotterdam, Netherlands
New Zealand
Research Site
Auckland, New Zealand
Research Site
Christchurch, New Zealand
Research Site
Wellington South, New Zealand
Norway
Research Site
Oslo, Norway
Poland
Research Site
Lodz, Poland
Research Site
Lublin, Poland
Research Site
Warszawa, Poland, 02-097
Research Site
Warszawa, Poland, 00-909
Research Site
Warszawa, Poland, 00-957
Romania
Research Site
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, 129128
Research Site
Moscow, Russian Federation, 125167
Research Site
Moscow, Russian Federation, 115478
Research Site
Obninsk, Russian Federation, 249036
Research Site
Samara, Russian Federation, 443095
Research Site
St. Petersburg, Russian Federation, 193024
Research Site
St. Petersburg, Russian Federation, 197110
Research Site
St. Petersburg, Russian Federation, 197089
Research Site
St. Petersburg, Russian Federation, 194291
Spain
Research Site
Madrid, Spain, 28041
Research Site
Madrid, Spain, 28006
Research Site
Salamanca, Spain
Research Site
Zaragoza, Spain
Sweden
Research Site
Linkoping, Sweden
Research Site
Stockholm, Sweden
United Kingdom
Research Site
Bournemouth, United Kingdom
Research Site
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
  More Information

Additional Information:
No publications provided by Hoffmann-La Roche

Additional 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
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 August 26, 2014