A Study to Compare Mabthera (Rituximab), Fludarabine and Cyclophosphamide to Mabthera and Chlorambucil in Participants With Chronic Lymphocytic Leukemia and Unfavorable Somatic Status

Prospective Randomized Study to Compare Efficacy and Safety of RFC-Lite (Rituximab, Fludarabine, Cyclophosphamide) Regimen With LR (Rituximab, Chlorambucil) as a First-Line Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia and Unfavorable Somatic Status

This multi-center, randomized study compared the efficacy and safety of MabThera (rituximab) in combination with either fludarabine and cyclophosphamide or with chlorambucil in participants with previously untreated B-cell chronic lymphocytic leukemia and unfavorable somatic status. Participants were randomized to receive Mabthera (375 mg/m2 intravenously [IV] Day 1 of Cycle 1, 500 mg/m2 IV Day 1 Cycles 2-6) with either fludarabine (20 mg/m2 IV or 32 mg/m2 orally Days 1-3) and cyclophosphamide (150 mg/m2 IV or orally Days 1-3) or with chlorambucil (10 mg/m2 orally Days 1-7) for 6 cycles of 28 days. Anticipated time on study treatment was 24 weeks.

Study Overview

• Status: Terminated
• Conditions: Lymphocytic Leukemia, Chronic
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab; Drug: Chlorambucil

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Irkutsk, Russian Federation, 664079
    • The order of Honour pin Irkutsk regional clinical hospital; Hematology Department
  • Kemerovo, Russian Federation, 650066
    • Kemerovo Regional Clinical Hospital
  • Moscow, Russian Federation, 115478
    • N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
  • Moscow, Russian Federation, 125284
    • City Clinical Botkin's Hospital; City Hematological Center
  • Saint-Petersburg, Russian Federation, 198205
    • City Clinical Hospital #15; Hematology department
  • St. Petersburg, Russian Federation, 197110
    • Saint-Petersburg SHI City Clinical Hospital #31
  • Tula, Russian Federation, 300053
    • GUZ Tula Regioanal Clinical Hospital; Hematology
  • UFA, Russian Federation, 450005
    • Republican Clinical Hospital named after G.G. Kuvatov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients, 60-70 or >70 years of age
• Cumulative Illness Rating Scale (CIRS) comorbidity score >/=7 if patient is 60-70 years old
• Previously untreated B-cell chronic lymphocytic leukemia
• Binet stage B, C or A with progression
• ECOG performance status 0-2

Exclusion Criteria:

• Small-cell lymphoma
• Autoimmune hemolytic anemia
• Concomitant malignant disease during enrollment, except for basal cell carcinoma of the skin
• Chemotherapy for concomitant malignant disease within 12 months prior to study enrollment
• Richter's syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FCR-lite; Rituximab, fludarabine, and cyclophosphamide	Drug: Cyclophosphamide; 150 mg/m^2 IV or orally on Days 1-3 of each 28-day cycle for 6 cycles; Drug: Fludarabine; 20 mg/m^2 IV or 32 mg/m2 orally Days 1-3 of each 28-day cycle for 6 cycles; Drug: Rituximab; 375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles); Other Names: MabThera
Active Comparator: LR Therapy; Rituximab and chlorambucile	Drug: Rituximab; 375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles); Other Names: MabThera; Drug: Chlorambucil; 10 mg/m^2 orally on Days 1-7 of each 28-day cycle for 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Complete Remission	Complete remission was defined as the disappearance of all signs of disease.	Up to approximately 5 years
Percentage of Participants With Disease Progression	Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.	Up to approximately 5 years
Percentage of Participants With Stable Disease	Stable disease was defined as not meeting the criteria for partial remission or disease progression	Up to approximately 5 years
Percentage of Participants With Partial Remission	Partial remission was defined as a reduction in tumor size by >50%.	Up to approximately 5 years
Duration of Response	Duration of Response was defined as the time period from the last day of study treatment to the day when disease progression occurred in participants who previously had complete or partial remission. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. Complete remission was defined as the disappearance of all signs of disease. Partial remission was defined as a reduction in tumor size by >50%.	Up to approximately 5 years
Progression-free Survival	Progression-free survival was defined as the time period from the first day of study treatment to the day when disease progression occurred. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.	Up to approximately 5 years
Event-free Survival	Event-free survival was defined as the time period from the first day of study treatment to occurrence of any of the following events: appearance of disease progression or relapse; prescription of a new treatment for disease relapse; death caused by B-cell chronic lymphocytic leukemia (B-CLL); or complications from B-CLL or therapy. Relapse was defined as disease progression in participants with complete or partial remission lasting at least 6 months after treatment completion. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. Complete remission was defined as the disappearance of all signs of disease. Partial remission was defined as a reduction in tumor size by >50%.	Up to approximately 5 years
Overall Survival	Overall survival was defined as the time period from the first day of study treatment to participant death.	Up to approximately 5 years
Percentage of Participants With Phenotypic Remission	Phenotypic remission was considered achieved if a participant had a negative test for minimal residual disease. A negative test for minimal residual disease was defined as tumor cells ≤0.01% of the total number of peripheral leukocytes.	Up to approximately 5 years
Percentage of Participants With Adverse Events (AEs) and Serious AEs	An AE was defined as any unfavorable medical occurrence in a participant receiving a study drug, regardless of relationship the study drug. An AE was considered serious if it met any of the following criteria: was fatal or life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was clinically significant and/or required an intervention to prevent any of the listed criteria.	Up to approximately 5 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2011
• Primary Completion (Actual): March 16, 2016
• Study Completion (Actual): March 16, 2016

Study Registration Dates

• First Submitted: January 18, 2011
• First Submitted That Met QC Criteria: January 24, 2011
• First Posted (Estimate): January 26, 2011

Study Record Updates

• Last Update Posted (Actual): March 14, 2019
• Last Update Submitted That Met QC Criteria: November 23, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Rituximab; Fludarabine; Chlorambucil
• Other Study ID Numbers: ML25137

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No