A Study of Rituximab in Combination With Fludarabine and Cyclophosphamide in Participants With Chronic Lymphocytic Leukemia and Favorable Somatic Status

Prospective Study of Efficacy and Safety of RFC (Rituximab, Fludarabine, Cyclophosphamide) Regimen as a First-Line Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia and Favorable Somatic Status

This multi-center, single-arm study evaluated the efficacy and safety of rituximab in combination with fludarabine and cyclophosphamide in participants with B-cell chronic lymphocytic leukemia (CLL) and favorable somatic status.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 89
• 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
  • Krasnodar, Russian Federation, 350040
    • Regional Clinical Oncology Despensary #1; Hematology Department
  • Moscow, Russian Federation, 125101
    • City Clinical Hospital After Botkin; Hematology
  • Moscow, Russian Federation, 115478
    • N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
  • Saint-Petersburg, Russian Federation, 198205
    • City Clinical Hospital #15; Hematology department
  • St Petersburg, Russian Federation
    • Leningrad Regional Clinical Hospital; Hematology #1
  • 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: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of previously untreated B-cell CLL confirmed immunophenotypically
• For participants, age 60-70 years: Cumulative Illness Rating Scale (CIRS) comorbidity score less than or equal to (</=) 6
• Binet stage B, C or A with progression
• Life expectancy greater than or equal to (>/=) 12 months
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
• Women of child bearing potential and men should agree to use highly reliable contraceptive method throughout the treatment period and within 12 months after treatment completion

Exclusion Criteria:

• Participants with small-cell lymphoma
• Participants with auto-immune hemolytic anemia
• Concomitant malignant disease during enrollment, except basal cell carcinoma of the skin
• Chemotherapy for concomitant malignant disease given within 12 months prior to study enrollment
• Participants with Richter's Syndrome
• Participants with symptomatic Hepatitis B infection
• Any clinically significant infection that could not be cured prior to enrollment, including Human Immunodeficiency Virus (HIV) infection
• Creatinine clearance less than (<) 30 milliliters per minute (mL/min)
• Participants with congestive heart failure (CHF) New York Heart Association (NYHA) III-IV
• Participants with liver failure and acute hepatitis of any etiology
• Any other medical or mental condition which may preclude from receiving the entire course of protocol specified treatment or signing the informed consent
• History of an anaphylactic reaction to murine antibodies, proteins, or any other ingredient of rituximab
• Pregnancy and breast-feeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Rituximab + Fludarabine + Cyclophosphamide; Participants received rituximab 375 milligrams per square meter (mg/m^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m^2 IV or 40 mg/m^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m^2 IV or 250 mg/m^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Drug: Cyclophosphamide; Participants received cyclophosphamide 250 mg/m^2 IV or 250 mg/m^2 orally on Days 1-3 of each cycle.; Drug: Fludarabine; Participants received fludarabine 25 mg/m^2 IV or 40 mg/m^2 orally on Days 1-3 of each cycle.; Drug: Rituximab; Participants received 375 mg/m^2 IV on Day 1 of Cycle 1, then 500 mg/m^2 IV on Day 1 of each subsequent cycle.; Other Names: MabThera

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): June 17, 2011
• Primary Completion (Actual): May 4, 2016
• Study Completion (Actual): May 4, 2016

Study Registration Dates

• First Submitted: January 4, 2011
• First Submitted That Met QC Criteria: January 4, 2011
• First Posted (Estimate): January 6, 2011

Study Record Updates

• Last Update Posted (Actual): March 20, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2017
• Last Verified: August 1, 2017

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
• Other Study ID Numbers: ML25136

Drug and device information, study documents

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