A Study to Assess the Effect of Maintenance Treatment With Rituximab Versus No Treatment in Participants With Progressive B-Cell Chronic Lymphocytic Leukemia (CLL)

NCT00718549 | Completed Phase 3 Results DMC

• 2 other identifiers: ML212832008-001140-39
• Study Type: interventional
• Target: 128
• Locations: 2 countries
• Sites: 6

Brief Summary

This study will assess the effect of maintenance treatment with rituximab in comparison with observation period (no treatment), in participants with progressive B-cell CLL who have had previous first-line induction treatment with rituximab, cladribine and cyclophosphamide (RCC regimen). After 6 months of RCC induction therapy, participants will be randomized either to receive maintenance treatment with rituximab or to receive no treatment (observation only) for 96 weeks. Participants completing maintenance/observation period will be followed-up for approximately 3 years.

Conditions

Lymphocytic Leukemia, Chronic

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Disease Progression (PD), Relapse, or Death Due to Any Cause Assessed According to the National Cancer Institute (NCI) Revised Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL)

  PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (greater than \[\>\]1.5 centimeters \[cm\]), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of greater than or equal to (\>/=) 50 percent (%) in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by \>/=50%; an increase in the number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000 per microliter (/mcL); transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.

  From randomization to PD, Relapse, or death due to any cause (overall approximately 5 years)

• Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL

  PFS was defined as the time from date of randomization to date of PD, relapse, or death due to any cause. Participants alive with no evidence of PD or relapse were censored at date of last clinical examination. PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (\>1.5 cm), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of \>/=50% in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by \>/=50%; an increase in the number of blood lymphocytes by \>/=50% with B-lymphocytes \>/=5000/mcL; transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.

  From randomization to PD, relapse, or death due to any cause (overall approximately 5 years)

Secondary Outcomes (7)

• Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL

  8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129)

• Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR

  8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129)

• PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors

  From randomization to PD, relapse, or death due to any cause (overall approximately 5 years)

• Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29

  8 weeks after the last dose of rituximab during induction treatment (Week 29)

• Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129

  12 weeks after the end of maintenance treatment or observation phase (Week 129)

Study Arms (3)

Induction: Rituximab, Cladribine, Cyclophosphamide

EXPERIMENTAL

Participants will receive rituximab at a dose of 375 milligrams per meter squared (mg/m\^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 will be administered in Cycles 2-6. Each cycle will be of 28 days in duration.

Drug: Cladribine; Drug: Cyclophosphamide; Drug: Rituximab

Maintenance Arm: Rituximab

EXPERIMENTAL

Participants with PR or CR after induction phase who will be randomized to maintenance arm will receive rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants will receive rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).

Drug: Rituximab

Observation Arm: No Intervention

NO INTERVENTION

Participants with PR or CR after induction phase who will be randomized to observation arm will not receive any intervention. Participants will be assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.

Interventions

Cladribine DRUG

Cladribine will be adminiatered at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4 of each 28-day cycle during induction phase.

Induction: Rituximab, Cladribine, Cyclophosphamide

Cyclophosphamide DRUG

Cyclophosphamide will be administred at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 of each 28-day cycle during induction phase.

Induction: Rituximab, Cladribine, Cyclophosphamide

Rituximab DRUG

Rituximab will be administered at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 during induction phase. Rituximab will be administered at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle during maintenance phase.

Also known as: MabThera

Induction: Rituximab, Cladribine, Cyclophosphamide; Maintenance Arm: Rituximab

Eligibility Criteria

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

You may qualify if:

• Immunologically confirmed diagnosis of B-cell CLL
• Rai stage I-IV disease with evidence of progression
• No previous chemotherapy, radiotherapy, or immunotherapy for B-cell CLL
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

You may not qualify if:

• Active secondary malignancy or transformation to aggressive lymphoma
• Medical condition requiring chronic use of oral corticosteroids at a dose of 1 mg/kg or 60 mg/m\^2 over 2 weeks
• History of other malignancies within 2 years before study entry, except for dequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone with curative intent

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (6)

City Clinical Hospital #9

Minsk, 220116, Belarus

Location

Medical University, Independent Public Clinical Hospital; Dept. of Hematology, SPSK

Bialystok, 15-276, Poland

Location

Szpital Uniwersytecki W Krakowie; Klinika Hematologii

Krakow, 31-501, Poland

Location

Medical University School; Dept. of Haematology

Lodz, 93-510, Poland

Location

Istytut Hematologii i Transfuzjologii; Hematologia

Warsaw, 02 776, Poland

Location

Medical Uni of Wroclaw; Hematology

Wroclaw, 50-367, Poland

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Cladribine; Cyclophosphamide; 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)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; 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

Limitations and Caveats

In 2011 the recruitment was stopped due to low enrollment rate, and in 2015 the trial was prematurely discontinued.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2008
• First Posted: July 18, 2008
• Study Start: July 21, 2009
• Primary Completion: September 14, 2015
• Study Completion: September 14, 2015
• Last Updated: August 20, 2018
• Results First Posted: August 20, 2018

Record last verified: 2017-11

Locations

BE (1); PL (5)