A Phase III Randomized Trial to Evaluate the Efficacy and Safety of Second-Line Therapy With Fludarabine Plus Alemtuzumab vs. Fludarabine Alone in Patients With B-Cell Chronic Lymphocytic Leukemia

Genzyme, a Sanofi Company48 sites in 15 countries335 target enrollmentJuly 2004

ConditionsB-Cell Chronic Lymphocytic Leukemia

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: B-Cell Chronic Lymphocytic Leukemia
Sponsor: Genzyme, a Sanofi Company
Enrollment: 335
Locations: 48
Primary Endpoint: Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment
Status: Completed
Last Updated: 12 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 3, prospective, multicenter, open-label, randomized, controlled study to evaluate and compare the efficacy and safety of fludarabine plus alemtuzumab versus fludarabine alone as second-line therapy for patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). Patients who meet all eligibility criteria and sign the informed consent document may be entered on the study.

Registry

clinicaltrials.gov

Start Date

July 2004

End Date

June 2010

Last Updated

12 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Genzyme, a Sanofi Company

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•A diagnosis of B-cell chronic lymphocytic leukemia (B-CLL); according to the National Cancer Institute Working Group (NCI WG) criteria.
•Relapsed or refractory disease after 1 prior regimen except patients who were refractory to (i.e., progressed on) fludarabine or alemtuzumab therapy. Patients who previously responded (complete response or partial response) to fludarabine or alemtuzumab therapy, but who have relapsed at the time of study entry, may be eligible but response to fludarabine or alemtuzumab therapy must have lasted \>12 months (i.e., \>12 months from a documented response to a documented relapse).
•Binet stage A, stage B, or stage C or Rai Stage I through IV disease with evidence of progression as evidenced by the presence of one or more of the following:
•I. Evidence of progressive marrow failure as manifested by: 1) a decrease in hemoglobin to \<11g/dL, or 2) a decrease in platelet count to \<100 x 10\^9/L within the previous 6 months, or 3) a decrease in absolute neutrophil count (ANC) to \<1.0 X 10\^9/L.
•II. Progressive splenomegaly to \>2 cm below the left costal margin or other organomegaly.
•III. Progressive lymphadenopathy.
•IV. Progressive lymphocytosis with an increase of 50% over a 2-month period, or an anticipated doubling time of less than 6 months.
•World Health Organization (WHO) performance status (PS) of 0 or
•Life expectancy \>12 weeks.
•Anti-cancer therapy, major surgery, or irradiation was completed \>3 weeks before randomization in this study. Patient must have recovered from the acute side effects incurred as a result of previous therapy.

Exclusion Criteria

•Previously treated with \>1 prior regimen for B-CLL.
•Previously treated with a fludarabine plus alemtuzumab (FluCAM) regimen for B-CLL.
•Positive Coombs test and actively hemolyzing.
•Absolute neutrophil count (ANC) \<1.5 x 10\^9/L or platelet count \<75 x 10\^9/L, unless due to bone marrow involvement.
•Medical condition requiring chronic use of pharmacologic doses of oral corticosteroids, i.e. anything other than replacement dose levels.
•History of anaphylaxis following exposure to monoclonal antibodies.
•Use of investigational agents within 6 weeks prior to study randomization.
•Active infection or history of severe infection (grade 4) within 3 months prior to study randomization.
•Known to be human immunodeficiency virus (HIV) positive.
•Autoimmune thrombocytopenia.

Outcomes

Primary Outcomes

Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment

Time Frame: Up to 6 years

Progression-free survival was defined as the number of days from the date of randomization to the date of first objective documentation of progressive disease (PD) as determined by the treatment-blinded IRRP, or death due to any cause. Results are expressed in months.

Secondary Outcomes

Participant Best Response to Treatment Assessed by the Independent Response Review Panel (IRRP)(Up to 9 months)
Mean EQ-5D™ Index Scores to Measure Quality of Life at End of Treatment(up to month 6 (end of treatment))
Kaplan-Meier Estimates of Overall Survival Time(Up to 6 years)
Kaplan Meier Estimates for Time to Disease Progression Assessed by the Independent Response Review Panel (IRRP)(Up to 6 years)
Kaplan-Meier Estimates for Duration of Response Assessed by the Independent Response Review Panel (IRRP)(Up to 6 years)
Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at Baseline(Day 0 (baseline))
Kaplan-Meier Estimates for Time to Alternative Therapy(Up to 6 years)
Mean EQ-5D™ Index Scores to Measure Quality of Life at Baseline(Day 0 (baseline))
Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at End of Treatment(up to month 6 (end of treatment))
Summary of Participants With Adverse Experiences (AEs)(Up to 6 years)
Mean Systemic Clearance (CL) of Fludarabine(month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion))
Total Volume of Distribution (Vss) of Fludarabine(month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion))
Maximum Plasma Concentration (Cmax) of Fludarabine(month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion))
Area Under the Curve (AUC) of Fludarabine From (AUC 0-tau)(month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion))
Participants With Minimal Residual Disease (MRD)(up to 9 months)