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

Lymphocytic Leukemia, Chronic Clinical Trial

Official title:

Prospective Randomized Study to Compare Efficacy and Safety of RFC-Lite (Rituximab, Fludarabine, Cyclophosphamide) Regimen With LR (Rituximab, Chlorambucil) as a First-Line Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia and Unfavorable Somatic Status

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01283386
• Other study ID #: ML25137
• Status: Terminated
• Phase: Phase 4
• Start date: April 27, 2011
• Est. completion date: March 16, 2016

Study information

• Verified date: November 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: March 16, 2016
• Est. primary completion date: March 16, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphocytic Leukemia, Chronic

Intervention

Drug:
• Chlorambucil
10 mg/m^2 orally on Days 1-7 of each 28-day cycle for 6 cycles
• Cyclophosphamide
150 mg/m^2 IV or orally on Days 1-3 of each 28-day cycle for 6 cycles
• Fludarabine
20 mg/m^2 IV or 32 mg/m2 orally Days 1-3 of each 28-day cycle for 6 cycles
• Rituximab
375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles)

Locations

Country	Name	City	State
Russian Federation	The order of Honour pin Irkutsk regional clinical hospital; Hematology Department	Irkutsk
Russian Federation	Kemerovo Regional Clinical Hospital	Kemerovo
Russian Federation	City Clinical Botkin's Hospital; City Hematological Center	Moscow
Russian Federation	N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis	Moscow
Russian Federation	City Clinical Hospital #15; Hematology department	Saint-Petersburg
Russian Federation	Saint-Petersburg SHI City Clinical Hospital #31	St. Petersburg
Russian Federation	GUZ Tula Regioanal Clinical Hospital; Hematology	Tula
Russian Federation	Republican clinical hospital named after G.G. Kuvatov	UFA

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Complete Remission	Complete remission was defined as the disappearance of all signs of disease.	Up to approximately 5 years
Primary	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
Primary	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
Primary	Percentage of Participants With Partial Remission	Partial remission was defined as a reduction in tumor size by >50%.	Up to approximately 5 years
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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