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

NCT02533401 | Completed Phase 2 Results

• 1 other identifier: ML18429
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 9

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.

Conditions

Lymphocytic Leukemia, Chronic

Outcome Measures

Primary Outcomes (5)

• 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)

Study Arms (1)

Rituximab + Fludarabine + Cyclophosphamide

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Rituximab

Interventions

Cyclophosphamide DRUG

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.

Rituximab + Fludarabine + Cyclophosphamide

Fludarabine DRUG

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.

Rituximab + Fludarabine + Cyclophosphamide

Rituximab DRUG

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.

Also known as: MabThera/Rituxan

Rituximab + Fludarabine + Cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (9)

Unknown Facility

Buenos Aires, 1406, Argentina

Location

Unknown Facility

Buenos Aires, C1114AAN, Argentina

Location

Unknown Facility

Buenos Aires, C1280AEB, Argentina

Location

Unknown Facility

Buenos Aires, C1431FWO, Argentina

Location

Unknown Facility

Córdoba, 5016, Argentina

Location

Unknown Facility

La Plata, B1897GOL, Argentina

Location

Unknown Facility

Pilar, B1629ODT, Argentina

Location

Unknown Facility

Rosario, S2000DSV, Argentina

Location

Unknown Facility

Caracas, 2122, Venezuela

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Cyclophosphamide; fludarabine; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2015
• First Posted: August 26, 2015
• Study Start: February 1, 2006
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 2, 2016
• Results First Posted: May 2, 2016

Record last verified: 2016-03

Locations

AR (8); VE (1)