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

• ClinicalTrials.gov Identifier: NCT02533401
• Recruitment Status: Completed
• First Posted: August 26, 2015
• Results First Posted: May 2, 2016
• Last Update Posted: May 2, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Lymphocytic Leukemia, Chronic	Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: February 2006
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: December 2014

Arms and Interventions

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 Name: MabThera/Rituxan

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Death or Disease Progression [ Time Frame: Up to 5 years (from Baseline until disease progression or death, whichever occurred first) ]
   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.
2. Progression-Free Survival (PFS) [ Time Frame: Up to 5 years (from Baseline until disease progression or death, whichever occurred first) ]
   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.
3. Percentage of Participants Who Died [ Time Frame: Up to 5 years (from Baseline until death) ]
   Participants were followed for survival throughout the study. The percentage of participants who died of any cause during the study was calculated.
4. Overall Survival (OS) [ Time Frame: Up to 5 years (from Baseline until death) ]
   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
5. Percentage of Participants With Complete Response (CR), Nodular Partial Response (nPR), or Partial Response (PR) [ Time Frame: 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) ]
   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.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

Argentina

Buenos Aires, Argentina, 1406

Buenos Aires, Argentina, C1114AAN

Buenos Aires, Argentina, C1280AEB

Buenos Aires, Argentina, C1431FWO

Córdoba, Argentina, 5016

La Plata, Argentina, B1897GOL

Pilar, Argentina, B1629ODT

Rosario, Argentina, S2000DSV

Venezuela

Caracas, Venezuela, 2122

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02533401
• Other Study ID Numbers: ML18429
• First Posted: August 26, 2015
• Results First Posted: May 2, 2016
• Last Update Posted: May 2, 2016
• Last Verified: March 2016

Additional relevant MeSH terms:

Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Cyclophosphamide; Rituximab; Fludarabine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological