A Study of Rituximab (MabThera) in Participants With Chronic Lymphocytic Leukemia (CLL)

A Multicenter, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of Rituximab Plus Fludarabine and Cyclophosphamide (FCR) as First-Line Treatment in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)

This study will evaluate the efficacy and safety of rituximab in combination with chemotherapy (fludarabine and cyclophosphamide) in participants with B-cell CLL.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB
  • Buenos Aires, Argentina, 1406
  • Buenos Aires, Argentina, C1114AAN
  • Buenos Aires, Argentina, C1431FWO
  • Córdoba, Argentina, 5016
  • La Plata, Argentina, B1897GOL
  • Pilar, Argentina, B1629ODT
  • Rosario, Argentina, S2000DSV
• Venezuela
  • Caracas, Venezuela, 2122

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult participants greater than or equal to (≥) 18 years of age
• B-cell CLL
• No previous treatment for leukemia

Exclusion Criteria:

• History of other malignancies within 2 years before study entry, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, prostate cancer, or breast cancer
• Comorbid condition requiring long-term (greater than [>] 1 month) systemic corticosteroids during study treatment
• Known infection with hepatitis B or C virus or with human immunodeficiency virus (HIV)

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 will receive rituximab (375 milligrams per meter-squared [mg/m^2] intravenously [IV]) on Cycle 1 Day 1, followed by fludarabine (25 mg/m^2 once daily IV) and cyclophosphamide (250 mg/m^2 once daily IV) for Days 2 to 4 of Cycle 1. Then rituximab (500 mg/m^2 IV) will be administered on Day 1 of Cycles 2 to 6, followed by IV fludarabine (25 mg/m^2 once daily IV) and cyclophosphamide (250 mg/m^2 once daily IV) on Days 1 to 3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length, and the overall duration of treatment will be approximately 6 months.

Drug: Cyclophosphamide; Cyclophosphamide will be administered IV at 250 mg/m^2/day on Day 2-4 of Cycle 1 and then on Day 1-3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.; Drug: Fludarabine; Fludarabine will be administered IV at 25 mg/m^2/day on Day 2-4 of Cycle 1 and then on Day 1-3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.; Drug: Rituximab; Rituximab will be administered IV at 375 mg/m^2 on Day 1 of Cycle 1 and then at 500 mg/m^2 on Day 1 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.; Other Names: MabThera/Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Death or Disease Progression	Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: greater than or equal to (≥) 50 percent (%) increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 centimeters (cm) from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. The percentage of participants with death or documented disease progression at any time during the study was calculated.	Up to 5 years (from Baseline until disease progression or death, whichever occurred first)
Progression-Free Survival (PFS)	Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: ≥50% increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 cm from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. PFS was defined as the time from study inclusion until first event of disease progression or death and was estimated using Kaplan-Meier analysis.	Up to 5 years (from Baseline until disease progression or death, whichever occurred first)
Percentage of Participants Who Died	Participants were followed for survival throughout the study. The percentage of participants who died of any cause during the study was calculated.	Up to 5 years (from Baseline until death)
Overall Survival (OS)	Participants were followed for survival throughout the study. OS was defined as the time from study inclusion until death from any cause and was estimated using Kaplan-Meier analysis	Up to 5 years (from Baseline until death)
Percentage of Participants With Complete Response (CR), Nodular Partial Response (nPR), or Partial Response (PR)	Treatment response was monitored throughout the study and assessed using standardized criteria. CR was defined as hemoglobin ≥11 grams per deciliter (g/dL), lymphocytes less than (<) 4000 cells per cubic millimeter (cells/mm^3), neutrophils greater than (>) 1500 cells/mm^3, platelets >100,000 cells/mm^3, bone marrow (BM) biopsy with <30% lymphocytes with no lymphocytic infiltrates, no evidence of lymphoid nodules on physical exam, and performance status of 0. PR was defined as >50% decrease in size of enlarged lymph nodes, hepatomegaly, and splenomegaly, with peripheral counts meeting the same criteria as CR or ≥50% improvement from pre-treatment values. Participants with lymphoid nodules on BM biopsy who otherwise met CR criteria were considered nPR. The percentage of participants with each level of best overall response was calculated.	Up to 4 years (assessed every 3 months during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 24, 2015
• First Submitted That Met QC Criteria: August 24, 2015
• First Posted (Estimate): August 26, 2015

Study Record Updates

• Last Update Posted (Estimate): May 2, 2016
• Last Update Submitted That Met QC Criteria: March 30, 2016
• Last Verified: March 1, 2016

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: ML18429