Overview

This trial is active, not recruiting.

Condition leukaemia, lymphocytic, chronic
Treatments chlorambucil, tablets, ofatumumab (gsk1841157) infusion
Phase phase 3
Sponsor GlaxoSmithKline
Start date December 2008
End date March 2013
Trial size 447 participants
Trial identifier NCT00748189, OMB110911

Summary

The purpose of this study is to evaluate the safety and efficacy of ofatumumab added to chlorambucil in patients with untreated Chronic Lymphocytic Leukemia.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
ofatumumab dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles
chlorambucil, tablets
2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles
ofatumumab (gsk1841157) infusion ofatumumab (GSK1841157) infusion
iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;
(Active Comparator)
chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles
chlorambucil, tablets
2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

Primary Outcomes

Measure
Progression-Free Survival (PFS), as Assessed by the Independent Review Committee (IRC)
time frame: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)

Secondary Outcomes

Measure
Number of Participants With the Best Overall Response (OR), as Assessed by the IRC
time frame: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)
Number of Participants Who Were Negative for Minimal Residual Disease (MRD)
time frame: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)
Overall Survival
time frame: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)
Time to Response, as Assessed by the IRC
time frame: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)
Duration of Response (DOR), as Assessed by the IRC
time frame: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)
Time to Progression, as Assessed by the IRC
time frame: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)
Time to Next Therapy
time frame: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)
Number of Participants With Improvement in ECOG Performance Status of 0 or 1, as Assessed by the IRC
time frame: Baseline, Cycle 3 Day 1, 1 month Follow-up
Number of Participants With Improvement in Constitutional Symptoms (CS)
time frame: Baseline, Cycle 3 Day 1, and 1 month Follow-up
Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result
time frame: Baseline, Cycle 4 Day 1, 1 Month Follow-up, and 6 Month Follow-up
Cmax and Ctrough of Ofatumumab
time frame: Cycle 1 Day 1,Cycle 1 Day 8, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, and Cycle 9 Day 1
Total Plasma Clearance (CL) of Ofatumumab
time frame: Cycle 4 Day 1
AUC(0-tau) of Ofatumumab
time frame: Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1
Vss of Ofatumumab
time frame: Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1
Plasma Half Life (t1/2) of Ofatumumab
time frame: Cycle 4 Day 1
Dose-normalized Cmax of Chlorambucil and Phenylacetic Acid Mustard (PAAM)
time frame: Cycle 3 Day 1
Dose-normalized AUC(0-6) and AUC(0-inf) of Chlorambucil and Dose-normalized AUC(0-6) of Phenylacetic Acid Mustard (PAAM)
time frame: Cycle 3 Day 1
Change From Baseline in Health Related Quality of Life (HRQOL)
time frame: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
time frame: From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy (Median follow-up approximately 29.3 months)
Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher
time frame: From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy (Median follow-up approximately 29.3 months)
Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia)
time frame: From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy (Median follow-up approximately 29.3 months)
Number of Participants With Autoimmune Hemolytic Anaemia (AIHA) Disease
time frame: From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy (Median follow-up approximately 29.3 months)
Number of Participants Who Recived no Transfusion or at Least One Transfusion During the Study
time frame: From start of treatment to the last study visit/withdrawal visit (Median follow-up approximately 29.3 months)
Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM
time frame: From start of treatment to the last study visit/withdrawal visit (Median follow-up approximately 29.3 months)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - confirmed CLL diagnosis and active CLL requiring treatment - considered inappropriate for fludarabine-based therapy - not been treated for CLL before - fully active at a minimum or fully capable of selfcare and up and about more than 50% of waking hours - age 18yrs or older - signed written informed consent Exclusion Criteria: - prior CLL therapy - abnormal/inadequate blood values, liver, and kidney function - certain heart problems, active or chronic infections, serious significant diseases, AIHA requiring treatment, other current cancer or within last 5 years - CLL transformation - CLL central nervous system involvement - current participation in other clinical study - inability to comply with the protocol activities - lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception

Additional Information

Official title A Phase III, Open Label, Randomized, Multicenter Trial of Ofatumumab Added to Chlorambucil Versus Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia
Description Chlorambucil, is currently approved for treatment of frontline chronic lymphocytic leukemia, especially, but not limited to the ailing and elderly patient population. Several other more aggressive treatment options are available (e.g. fludarabine), however they are not suitable for all CLL patients, especially the ailing and elderly, due to greater toxicity. Ofatumumab is effective with low toxicity. The addition of ofatumumab to chlorambucil offers potentially a more effective therapy, with limited toxicity. The objective of this study is to evaluate progression-free survival (PFS), overall response and overall survival in subjects with previously untreated CLL with ofatumumab added to chlorambucil versus chlorambucil.
Trial information was received from ClinicalTrials.gov and was last updated in February 2014.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.
Location data was received from the National Cancer Institute and was last updated in March 2016.