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

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

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01283386

Enrollment

Registered

2011-01-26

Start date

2011-04-27

Completion date

2016-03-16

Last updated

2019-03-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphocytic Leukemia, Chronic

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.

Interventions

DRUGChlorambucil

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

DRUGCyclophosphamide

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

DRUGFludarabine

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

DRUGRituximab

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

60 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Complete Remission	Up to approximately 5 years	Complete remission was defined as the disappearance of all signs of disease.
Percentage of Participants With Disease Progression	Up to approximately 5 years	Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.
Percentage of Participants With Stable Disease	Up to approximately 5 years	Stable disease was defined as not meeting the criteria for partial remission or disease progression
Percentage of Participants With Partial Remission	Up to approximately 5 years	Partial remission was defined as a reduction in tumor size by \>50%.
Duration of Response	Up to approximately 5 years	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%.
Progression-free Survival	Up to approximately 5 years	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.
Event-free Survival	Up to approximately 5 years	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%.
Overall Survival	Up to approximately 5 years	Overall survival was defined as the time period from the first day of study treatment to participant death.
Percentage of Participants With Phenotypic Remission	Up to approximately 5 years	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.
Percentage of Participants With Adverse Events (AEs) and Serious AEs	Up to approximately 5 years	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.

Countries

Russia

Participant flow

Participants by arm

Arm	Count
FCR-lite Rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1 (one cycle = 28 days), then 500 mg/m\^2 IV on Day 1 of each subsequent cycle for 6 cycles. When fludarabine / cyclophosphamide IV administered: fludarabine 20 mg/m\^2 IV on Days 1-3; cyclophosphamide 150 mg/m\^2 IV on Days 1-3. When fludarabine / cyclophosphamide orally administered: fludarabine 32 mg/m\^2 orally on Days 1-3; cyclophosphamide 150 mg/m\^2 orally on Days 1-3 for 6 cycles (28 days each).	10
LR Therapy Rituximab 375 mg/m\^2 IV on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle for 6 cycles. Chlorambucile 10 mg/m\^2 orally on Days 1-7 for 6 cycles.	16
Total	26

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	2	0
Overall Study	Progression of underlying disease	2	7
Overall Study	Protocol Violation	0	1
Overall Study	Reason not specified	1	0
Overall Study	Relapse of underlying disease	1	3
Overall Study	Withdrawal by Subject	2	1

Baseline characteristics

Characteristic	FCR-lite	LR Therapy	Total
Age, Continuous	68.7 years STANDARD_DEVIATION 7.09	68.6 years STANDARD_DEVIATION 4.95	68.6 years STANDARD_DEVIATION 5.73
Sex: Female, Male Female	3 Participants	7 Participants	10 Participants
Sex: Female, Male Male	7 Participants	9 Participants	16 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	8 / 10	9 / 16
serious Total, serious adverse events	2 / 10	3 / 16

Outcome results

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%.