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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00090051
• Other study ID #: 102-14
• Secondary ID: BO17072
• Status: Completed
• Phase: Phase 3
• First received: August 23, 2004
• Last updated: May 29, 2013
• Start date: July 2003
• Est. completion date: June 2012

Study information

• Verified date: May 2013
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 552
• Est. completion date: June 2012
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Rituximab
Intravenous repeating dose
• Fludarabine Phosphate
Intravenous repeating dose
• Cyclophosphamide
Intravenous repeating dose

Locations

Country	Name	City	State
Australia	Research Site	Concord
Australia	Research Site	East Melbourne
Australia	Research Site	Frankston
Belgium	Research Site	Antwerpen
Belgium	Research Site	Bruxelles
Belgium	Research Site	Leuven
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	St Johns	Newfoundland and Labrador
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Denmark	Research Site	Aarhus
Denmark	Research Site	Copenhagen
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	Research Site	Marseille Cedex 9
France	Research Site	Montpellier Cedex 5
France	Research Site	Nantes Cedex 1
France	Research Site	Paris
France	Research Site	Paris Cedex 04
France	Research Site	Paris Cedex 10
France	Research Site	Pierre Benite Cedex
France	Research Site	Rouen
France	Research Site	Tours
France	Research Site	Vandoeuvre
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Pecs
Hungary	Research Site	Szeged
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	Research Site	Vicenza
Netherlands	Research Site	Amersfoort
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Den Haag
Netherlands	Research Site	Rotterdam
New Zealand	Research Site	Auckland
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Wellington South
Norway	Research Site	Oslo
Poland	Research Site	Lodz
Poland	Research Site	Lublin
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Romania	Research Site	Bucharest
Romania	Research Site	Bucharest
Romania	Research Site	Tg. Mures
Romania	Research Site	Timisoara
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Samara
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Salamanca
Spain	Research Site	Zaragoza
Sweden	Research Site	Linkoping
Sweden	Research Site	Stockholm
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	Research Site	London
United Kingdom	Research Site	Wakefield
United States	Research Site	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Biogen, Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Hungary,  Italy,  Netherlands,  New Zealand,  Norway,  Poland,  Romania,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Mean observation time at time of analysis was approximately 26 months	No
Primary	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.	Mean observation time at time of analysis was approximately 26 months	No
Primary	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.	Median observation time was approximately 5 years	No
Secondary	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.	Mean observation time at time of analysis was approximately 26 months	No
Secondary	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.	Mean observation time at time of analysis was approximately 26 months	No
Secondary	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.	Mean observation time at time of analysis was approximately 26 months	No
Secondary	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.	Mean observation time at time of analysis was approximately 26 months	No
Secondary	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.	Mean observation time at time of analysis was approximately 26 months	No
Secondary	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.	Mean observation time at time of analysis was approximately 26 months	No
Secondary	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.	Median observation time was approximately 5 years	No
Secondary	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.	Median observation time was approximately 5 years	No
Secondary	Final Analysis: Percentage of Participants With Complete Response	Complete response was defined as the disappearance of all signs of cancer in response to treatment.	Median observation time was approximately 5 years	No
Secondary	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.	Median observation time was approximately 5 years	No
Secondary	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.	Median observation time was approximately 5 years	No
Secondary	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.	Median observation time was approximately 5 years	No

External Links

•   Clinical Study Report Synopsis