Last updated: 11/07/2018 03:08:25
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 GSK Clinical Study Register is no longer maintained for this study.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.

Phase II Study of Ofatumumab plus ifosfamide, carboplatin, etoposide (ICE) or dexamethasone, cytarabine, cisplatin (DHAP) chemotherapy regimen in relapsed/ refractory diffuse large B cell lymphoma (DLBCL)

GSK study ID
110927
See study documents
Clinicaltrials.gov ID
NCT00823719
See results summary
EudraCT ID
2009-010420-25
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 Single Arm, Safety and Efficacy Study of Ofatumumab in Combination with ICE or DHAP Chemotherapy in Relapsed or Refractory Aggressive Lymphoma Prior to Autologous Stem Cell Transplantation
Trial description: The purpose of this study is to evaluate the safety and efficacy of ofatumumab used in combination with ifosfamide, carboplatin, etoposide (ICE) or dexamethasone, cytarabine, cisplatin (DHAP) salvage chemotherapy regimens in subjects with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who are eligible for autologous stem cell transplant.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:

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

Timeframe: From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3

Secondary outcomes:

Number of participants with CR, as assessed by the Investigator

Timeframe: From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3

Number of participants with the ability to mobilize at least 2 million cluster of differentiation (CD)34+ cells per kilogram (kg) from peripheral blood

Timeframe: During treatment Cycle 2 (Study Days 22-42) and/or Cycle 3 (Study Days 43-63)

Progression-free survival (PFS)

Timeframe: From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3

Overall survival

Timeframe: From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3

Area under the concentration-time curve from time zero to infinity, AUC(0-inf), of ofatumumab at the first infusion (Cycle 1, Day 1) and the last infusion (Cycle 3)

Timeframe: Cycle 1 Day 1 (Study Day 1; up to 1 week) and Cycle 3 (Study Day 43; up to 6 weeks)

Area under the concentration-time curve during the dosing interval (AUC(0-tau)) of ofatumumab at the last infusion (Cycle 3)

Timeframe: Cycle 3 (Study Day 43; 3 weeks)

Clearance (CL) of ofatumumab

Timeframe: Study Day 1 up to Study Day 85 (up to 12 weeks)

Maximum plasma concentration (Cmax) of ofatumumab at the first infusion (Cycle 1 Day 1), second infusion (Cycle 1 Day 8), and last infusion (Cycle 3)

Timeframe: Cycle 1 Day 1 (Study Day 1; up to 48 hours), Cycle 1 Day 8 (Study Day 8; up to 24 hours), Cycle 3 (Study Day 43; up to 48 hours)

Trough plasma concentration (Ctrough) of ofatumumab prior to second infusion (Cycle 1 Day 8), third infusion (Cycle 2), and last infusion (Cycle 3)

Timeframe: Cycle 1 Day 8 (Study Day 8; up to 8 hours prior to infusion start), Cycle 2 (Study Day 22; up to 7 hours prior to infusion start), Cycle 3 (Study Day 43; up to 6 hours prior to infusion start)

Terminal phase half-life (t1/2) of ofatumumab

Timeframe: Study Day 1 up to Study Day 85 (up to 12 weeks)

Volume of distribution at steady state (Vss) of ofatumumab

Timeframe: Study Day 1 up to Study Day 85 (up to 12 weeks)

Number of participants who were positive and negative for human anti-human antibodies (HAHA) at the indicated time points

Timeframe: Study Day 1 up to approximately Study Day 63

Number of participants with the indicated adverse events (AEs) associated with neutropenia

Timeframe: Study Day 1 to approximately Study Day 63

Number of participants with the indicated AEs associated with decreased hemoglobin counts

Timeframe: Study Day 1 to approximately Study Day 63

Number of participants with the indicated AEs associated with decreased platelet counts

Timeframe: Study Day 1 to approximately Study Day 63

Interventions:
  • Drug: ofatumumab + ICE
  • Drug: ofatumumab + DHAP
    • Enrollment:
    61
    Primary completion date:
    2011-11-07
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    MJ Matasar, MS Czuczman, MA Rodriguez et al . Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013;122:499-506.
    Medical condition
    Lymphoma, Large-Cell, Diffuse
    Product
    ofatumumab
    Collaborators
    Not applicable
    Study date(s)
    May 2009 to July 2011
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Subjects with CD20 positive aggressive non-Hodgkin's lymphoma (NHL) including DLBCL, transformed follicular lymphoma (FL) & grade 3b FL.
    • Refractory to, or relapsed following, first-line treatment with rituximab combined with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.
    • Previous cancer therapy for lymphoma, with the exception of required rituximab/ anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to first-line therapy and / or as a maintenance therapy, or limited field radiotherapy (as defined by the protocol).
    • Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to start of study therapy.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Subjects with CD20 positive aggressive non-Hodgkin's lymphoma (NHL) including DLBCL, transformed follicular lymphoma (FL) & grade 3b FL. Refractory to, or relapsed following, first-line treatment with rituximab combined with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.
    • Computed tomography (CT) with involvement of 2 or more clearly demarcated lesions with a long axis > 1.5 centimeters (cm) and short axis ≥ 1.0 cm or 1 clearly demarcated lesion with a long axis >2.0 cm and short axis ≥1.0 cm.
    • Baseline [18F] fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.
    • Age 18 yrs or older.
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
    • Eligible for high dose chemotherapy and autologous stem cell transplant (ASCT).
    • Resolution of toxicities from first-line therapy to a grade that in the opinion of the investigator does not contraindicate study participation.
    • Signed written informed consent.
    Exclusion criteria:
    • Previous cancer therapy for lymphoma, with the exception of required rituximab/ anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to first-line therapy and / or as a maintenance therapy, or limited field radiotherapy (as defined by the protocol).
    • Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to start of study therapy.
    • Chronic Glucocorticoid use (limited acute use is allowed and defined by the protocol).
    • History of significant cerebrovascular disease.
    • Abnormal/ inadequate white blood cell (WBC) count, liver, and kidney function.
    • Clinically significant cardiac disease, active or chronic infections, serious significant diseases, other cancer within last 5 years.
    • Known or suspected hypersensitivity to study treatments.
    • Prior treatment with anti-CD20 monoclonal antibodies, at any time, or treated with other monoclonal antibodies within 3 months prior to start of study therapy, with the exception of rituximab in both instances.
    • Inability to comply with the protocol activities.
    • Pregnant or lactating women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception during and up to 1 year following dosing completion.

    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

    Results posted on ClinicalTrials.gov

    Recruitment status
    No longer a GSK study
    Actual primary completion date
    2011-11-07
    Actual study completion date
    2011-11-07

    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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