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

Prospective Study of Efficacy and Safety of RFC (Rituximab, Fludarabine, Cyclophosphamide) Regimen as a First-Line Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia and Favorable Somatic Status

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01271010

Enrollment

Registered

2011-01-06

Start date

2011-06-17

Completion date

2016-05-04

Last updated

2018-03-20

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, 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.

Interventions

DRUGCyclophosphamide

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

DRUGFludarabine

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

DRUGRituximab

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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

* 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

Exclusion criteria

* 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

Design outcomes

Primary

Measure	Time frame	Description
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%.
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.
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
Rituximab + Fludarabine + Cyclophosphamide 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.	89
Total	89

Arm

Count

Rituximab + Fludarabine + Cyclophosphamide

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.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	2
Overall Study	Disease progression	27
Overall Study	Progression and relapse of disease	1
Overall Study	Protocol Violation	1
Overall Study	Reason not specified	11
Overall Study	Start of new CLL therapy	1
Overall Study	Withdrawal by Subject	18

Baseline characteristics

Characteristic	Rituximab + Fludarabine + Cyclophosphamide
Age, Continuous	55.9 years STANDARD_DEVIATION 6.39
Sex: Female, Male Female	31 Participants
Sex: Female, Male Male	58 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	70 / 89
serious Total, serious adverse events	12 / 89

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%.