A Study of Rituximab in Combination With Fludarabine and Cyclophosphamide in Participants With Chronic Lymphocytic Leukemia and Favorable Somatic Status

NCT01271010 | Terminated Phase 4 Results

• 1 other identifier: ML25136
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 10

Brief Summary

This multi-center, single-arm study evaluated the efficacy and safety of rituximab in combination with fludarabine and cyclophosphamide in participants with B-cell chronic lymphocytic leukemia (CLL) and favorable somatic status.

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 (1)

Rituximab + Fludarabine + Cyclophosphamide

EXPERIMENTAL

Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

Interventions

Cyclophosphamide DRUG

Participants received cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle.

Rituximab + Fludarabine + Cyclophosphamide

Fludarabine DRUG

Participants received fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle.

Rituximab + Fludarabine + Cyclophosphamide

Rituximab DRUG

Participants received 375 mg/m\^2 IV on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle.

Also known as: MabThera

Rituximab + Fludarabine + Cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of previously untreated B-cell CLL confirmed immunophenotypically
• For participants, age 60-70 years: Cumulative Illness Rating Scale (CIRS) comorbidity score less than or equal to (\</=) 6
• Binet stage B, C or A with progression
• Life expectancy greater than or equal to (\>/=) 12 months
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
• Women of child bearing potential and men should agree to use highly reliable contraceptive method throughout the treatment period and within 12 months after treatment completion

You may not qualify if:

• Participants with small-cell lymphoma
• Participants with auto-immune hemolytic anemia
• Concomitant malignant disease during enrollment, except basal cell carcinoma of the skin
• Chemotherapy for concomitant malignant disease given within 12 months prior to study enrollment
• Participants with Richter's Syndrome
• Participants with symptomatic Hepatitis B infection
• Any clinically significant infection that could not be cured prior to enrollment, including Human Immunodeficiency Virus (HIV) infection
• Creatinine clearance less than (\<) 30 milliliters per minute (mL/min)
• Participants with congestive heart failure (CHF) New York Heart Association (NYHA) III-IV
• Participants with liver failure and acute hepatitis of any etiology
• Any other medical or mental condition which may preclude from receiving the entire course of protocol specified treatment or signing the informed consent
• History of an anaphylactic reaction to murine antibodies, proteins, or any other ingredient of rituximab
• Pregnancy and breast-feeding women

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (10)

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

Irkutsk, 664079, Russia

Location

Kemerovo Regional Clinical Hospital

Kemerovo, 650066, Russia

Location

Regional Clinical Oncology Despensary #1; Hematology Department

Krasnodar, 350040, Russia

Location

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

Moscow, 115478, Russia

Location

City Clinical Hospital After Botkin; Hematology

Moscow, 125101, 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

Leningrad Regional Clinical Hospital; Hematology #1

Saint Petersburg, 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

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

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2011
• First Posted: January 6, 2011
• Study Start: June 17, 2011
• Primary Completion: May 4, 2016
• Study Completion: May 4, 2016
• Last Updated: March 20, 2018
• Results First Posted: March 20, 2018

Record last verified: 2017-08

Locations

RU (10)