A Study to Compare Mabthera (Rituximab), Fludarabine and Cyclophosphamide to Mabthera and Chlorambucil in Participants With Chronic Lymphocytic Leukemia and Unfavorable Somatic Status

NCT01283386 | Terminated Phase 4 Results

• 1 other identifier: ML25137
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 8

Brief Summary

This multi-center, randomized study compared the efficacy and safety of MabThera (rituximab) in combination with either fludarabine and cyclophosphamide or with chlorambucil in participants with previously untreated B-cell chronic lymphocytic leukemia and unfavorable somatic status. Participants were randomized to receive Mabthera (375 mg/m2 intravenously \[IV\] Day 1 of Cycle 1, 500 mg/m2 IV Day 1 Cycles 2-6) with either fludarabine (20 mg/m2 IV or 32 mg/m2 orally Days 1-3) and cyclophosphamide (150 mg/m2 IV or orally Days 1-3) or with chlorambucil (10 mg/m2 orally Days 1-7) for 6 cycles of 28 days. Anticipated time on study treatment was 24 weeks.

Conditions

Lymphocytic Leukemia, Chronic

Outcome Measures

Primary Outcomes (10)

• 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

Study Arms (2)

FCR-lite

EXPERIMENTAL

Rituximab, fludarabine, and cyclophosphamide

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

LR Therapy

ACTIVE COMPARATOR

Rituximab and chlorambucile

Drug: Chlorambucil; Drug: Rituximab

Interventions

Chlorambucil DRUG

10 mg/m\^2 orally on Days 1-7 of each 28-day cycle for 6 cycles

LR Therapy

Cyclophosphamide DRUG

150 mg/m\^2 IV or orally on Days 1-3 of each 28-day cycle for 6 cycles

FCR-lite

Fludarabine DRUG

20 mg/m\^2 IV or 32 mg/m2 orally Days 1-3 of each 28-day cycle for 6 cycles

FCR-lite

Rituximab DRUG

375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles)

Also known as: MabThera

FCR-lite; LR Therapy

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients, 60-70 or \>70 years of age
• Cumulative Illness Rating Scale (CIRS) comorbidity score \>/=7 if patient is 60-70 years old
• Previously untreated B-cell chronic lymphocytic leukemia
• Binet stage B, C or A with progression
• ECOG performance status 0-2

You may not qualify if:

• Small-cell lymphoma
• Autoimmune hemolytic anemia
• Concomitant malignant disease during enrollment, except for basal cell carcinoma of the skin
• Chemotherapy for concomitant malignant disease within 12 months prior to study enrollment
• Richter's syndrome

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

The order of Honour pin Irkutsk regional clinical hospital; Hematology Department

Irkutsk, 664079, Russia

Location

Kemerovo Regional Clinical Hospital

Kemerovo, 650066, Russia

Location

N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis

Moscow, 115478, Russia

Location

City Clinical Botkin's Hospital; City Hematological Center

Moscow, 125284, Russia

Location

Saint-Petersburg SHI City Clinical Hospital #31

Saint Petersburg, 197110, Russia

Location

City Clinical Hospital #15; Hematology department

Saint Petersburg, 198205, Russia

Location

GUZ Tula Regioanal Clinical Hospital; Hematology

Tula, 300053, Russia

Location

Republican clinical hospital named after G.G. Kuvatov

Ufa, 450005, Russia

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Chlorambucil; 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)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramide Mustards; 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

1-800-821-8590

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 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2011
• First Posted: January 26, 2011
• Study Start: April 27, 2011
• Primary Completion: March 16, 2016
• Study Completion: March 16, 2016
• Last Updated: March 14, 2019
• Results First Posted: March 14, 2019

Record last verified: 2018-11

Locations

RU (8)