Last updated: 11/07/2018 18:03:36
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.

Ofatumumab + Chlorambucil vs. Chlorambucil Monotherapy in previously untreated patients with Chronic Lymphocytic LeukemiaCOMPLEMENT 1

GSK study ID
OMB110911
See study documents
Clinicaltrials.gov ID
NCT00748189
EudraCT ID
2008-004932-19
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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
Trial description: The purpose of this study is to evaluate the safety and efficacy of ofatumumab added to chlorambucil in patients with untreated Chronic Lymphocytic Leukemia.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:

Progression-Free Survival (PFS), as assessed by the Independent Review Committee (IRC)

Timeframe: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)

Secondary outcomes:

Duration of response (DOR), as assessed by the IRC

Timeframe: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)

Time to next therapy

Timeframe: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)

Dose-normalized AUC(0-6) and AUC(0-inf) of chlorambucil and dose-normalized AUC(0-6) of phenylacetic acid mustard (PAAM)

Timeframe: Cycle 3 Day 1

Change from Baseline in health related quality of life (HRQOL)

Timeframe: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)

Number of participants with the best overall response (OR), as assessed by the IRC

Timeframe: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)

Vss of ofatumumab

Timeframe: Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1

Number of participants who were negative for minimal residual disease (MRD)

Timeframe: 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)

Timeframe: 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)

Cmax and Ctrough of ofatumumab

Timeframe: 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

Number of participants who recived no transfusion or at least one transfusion during the study

Timeframe: From start of treatment to the last study visit/withdrawal visit (Median follow-up approximately 29.3 months)

Number of participants with at least one Grade 3/Grade 4 myelosuppression (anemia, neutropenia, and thrombocytopenia)

Timeframe: 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 a human anti-human antibody (HAHA) positive result

Timeframe: Baseline, Cycle 4 Day 1, 1 Month Follow-up, and 6 Month Follow-up

Number of participants with autoimmune hemolytic anaemia (AIHA) disease

Timeframe: 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)

Total plasma clearance (CL) of ofatumumab

Timeframe: Cycle 4 Day 1

Overall Survival

Timeframe: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)

Mean change from Baseline in the Immunoglobulin (Ig) antibodies IgA, IgG, and IgM

Timeframe: From start of treatment to the last study visit/withdrawal visit (Median follow-up approximately 29.3 months)

AUC(0-tau) of ofatumumab

Timeframe: Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1

Time to response, as assessed by the IRC

Timeframe: From randomization until the 259th PFS event occurred (Median follow-up approximately 29.3 months)

Time to progression, as assessed by the IRC

Timeframe: 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

Timeframe: Baseline, Cycle 3 Day 1, 1 month Follow-up

Plasma half life (t1/2) of ofatumumab

Timeframe: Cycle 4 Day 1

Number of participants with improvement in constitutional symptoms (CS)

Timeframe: Baseline, Cycle 3 Day 1, and 1 month Follow-up

Dose-normalized Cmax of chlorambucil and phenylacetic acid mustard (PAAM)

Timeframe: Cycle 3 Day 1

Number of participants with AEs and SAEs of maximum severity of grade 3 or higher

Timeframe: 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)

Interventions:
  • Drug: chlorambucil, tablets
  • Drug: ofatumumab (GSK1841157) infusion
    • Enrollment:
    447
    Primary completion date:
    2013-20-03
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, Doubek M, Panagiotidis P, Kimby E, Schuh A, Pettitt AR, Boyd T, Montillo M, Gupta IV, Wright O, Dixon I, Carey JL, Chang CN, Lisby S, McKeown A, Offner F, COMPLEMENT 1 Study Investigators.Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial.Lancet.2015;385(9980):1873-83
    Roxanne C. Jewell, Kevin Laubscher, Eric Lewis, Lei Fang, Zarina Gafoor, Jodi Carey, Astrid McKeown, Sarah West, Oliver Wright, Donna Sedoti, Iestyn Dixon, Scott Hottenstein, and Geoffrey Chan.Assessment of the Effect of Ofatumumab on Cardiac Repolarization.J Clin Pharmacol.2015;55(1):114-121
    Medical condition
    Leukaemia, Lymphocytic, Chronic
    Product
    chlorambucil, ofatumumab
    Collaborators
    Not applicable
    Study date(s)
    December 2008 to June 2022
    Type
    Interventional
    Phase
    2/3

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    none
    • confirmed CLL diagnosis and active CLL requiring treatment
    • considered inappropriate for fludarabine-based therapy
    • prior CLL therapy
    • abnormal/inadequate blood values, liver, and kidney function
    Inclusion and exclusion criteria
    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

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Refer to study documents

    Recruitment status
    No longer a GSK study
    Actual primary completion date
    2013-20-03
    Actual study completion date
    Not applicable

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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