A Study of Rituximab (MabThera) in Participants With Chronic Lymphocytic Leukemia (CLL)

A Multicenter, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of Rituximab Plus Fludarabine and Cyclophosphamide (FCR) as First-Line Treatment in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02533401

Enrollment

Registered

2015-08-26

Start date

2006-02-28

Completion date

2014-12-31

Last updated

2016-05-02

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 study will evaluate the efficacy and safety of rituximab in combination with chemotherapy (fludarabine and cyclophosphamide) in participants with B-cell CLL.

Interventions

DRUGCyclophosphamide

Cyclophosphamide will be administered IV at 250 mg/m\^2/day on Day 2-4 of Cycle 1 and then on Day 1-3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.

DRUGFludarabine

Fludarabine will be administered IV at 25 mg/m\^2/day on Day 2-4 of Cycle 1 and then on Day 1-3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.

DRUGRituximab

Rituximab will be administered IV at 375 mg/m\^2 on Day 1 of Cycle 1 and then at 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Adult participants greater than or equal to (≥) 18 years of age * B-cell CLL * No previous treatment for leukemia

Exclusion criteria

* History of other malignancies within 2 years before study entry, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, prostate cancer, or breast cancer * Comorbid condition requiring long-term (greater than \[\>\] 1 month) systemic corticosteroids during study treatment * Known infection with hepatitis B or C virus or with human immunodeficiency virus (HIV)

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Death or Disease Progression	Up to 5 years (from Baseline until disease progression or death, whichever occurred first)	Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: greater than or equal to (≥) 50 percent (%) increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 centimeters (cm) from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. The percentage of participants with death or documented disease progression at any time during the study was calculated.
Progression-Free Survival (PFS)	Up to 5 years (from Baseline until disease progression or death, whichever occurred first)	Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: ≥50% increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 cm from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. PFS was defined as the time from study inclusion until first event of disease progression or death and was estimated using Kaplan-Meier analysis.
Percentage of Participants Who Died	Up to 5 years (from Baseline until death)	Participants were followed for survival throughout the study. The percentage of participants who died of any cause during the study was calculated.
Overall Survival (OS)	Up to 5 years (from Baseline until death)	Participants were followed for survival throughout the study. OS was defined as the time from study inclusion until death from any cause and was estimated using Kaplan-Meier analysis
Percentage of Participants With Complete Response (CR), Nodular Partial Response (nPR), or Partial Response (PR)	Up to 4 years (assessed every 3 months during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up)	Treatment response was monitored throughout the study and assessed using standardized criteria. CR was defined as hemoglobin ≥11 grams per deciliter (g/dL), lymphocytes less than (\<) 4000 cells per cubic millimeter (cells/mm\^3), neutrophils greater than (\>) 1500 cells/mm\^3, platelets \>100,000 cells/mm\^3, bone marrow (BM) biopsy with \<30% lymphocytes with no lymphocytic infiltrates, no evidence of lymphoid nodules on physical exam, and performance status of 0. PR was defined as \>50% decrease in size of enlarged lymph nodes, hepatomegaly, and splenomegaly, with peripheral counts meeting the same criteria as CR or ≥50% improvement from pre-treatment values. Participants with lymphoid nodules on BM biopsy who otherwise met CR criteria were considered nPR. The percentage of participants with each level of best overall response was calculated.

Countries

Argentina, Venezuela

Participant flow

Participants by arm

Arm	Count
Rituximab + Fludarabine + Cyclophosphamide Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via IV infusion as 375 mg/m\^2 on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.	34
Total	34

Arm

Count

Rituximab + Fludarabine + Cyclophosphamide

Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via IV infusion as 375 mg/m\^2 on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event/Intercurrent Disease	3
Overall Study	Death	5
Overall Study	Insufficient Response/Progressed Disease	1
Overall Study	Lost to Follow-up	1
Overall Study	Violation of Selection Criteria	1

Baseline characteristics

Characteristic	Rituximab + Fludarabine + Cyclophosphamide
Age, Continuous	60.3 years STANDARD_DEVIATION 8.8
Sex: Female, Male Female	5 Participants
Sex: Female, Male Male	29 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	18 / 34
serious Total, serious adverse events	15 / 34

Outcome results

Primary

Overall Survival (OS)

Participants were followed for survival throughout the study. OS was defined as the time from study inclusion until death from any cause and was estimated using Kaplan-Meier analysis

Time frame: Up to 5 years (from Baseline until death)