No longer a GSK study

Study Description:

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 GSK Clinical Study Register is no longer maintained for this study.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.

This is a Phase II, open label, single arm, multi-centre study investigating the safety and efficacy of ofatumumab plus bendamustine in subjects with untreated or relapsed CLL. Each subject from the screening phase who is willing to participate in the study and is found eligible according to the inclusion and exclusion criteria will enter the treatment phase and will receive a maximum of 6 Cycles of study treatment (ofatumumab plus bendamustine). All subjects will receive 3 Cycles of study treatment (Cycles 1, 2 and 3). Eligibility to receive study treatment for Cycles 4, 5 and 6 will be assessed following the 3rd Cycle. Subjects who have achieved at least stable disease with acceptable toxicity following 3 Cycles of treatment will be eligible to continue to receive study treatments for a maximum of 3 further Cycles. In case of progressive disease, at, or at any time after the start of Cycle 4, subjects must discontinue further study treatment and move into the study’s follow-up period. During the treatment phase, all eligible subjects will be allocated to receive the following study treatments: 1. Subjects with Untreated CLL: Up to 6 monthly intravenous infusions of ofatumumab (Cycle 1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 Days) in combination with up to 6 Cycles of intravenously infused bendamustine (90 mg/m2, Days 1 and 2, every 28 Days). 2. Subjects with Relapsed CLL: Up to 6 monthly intravenous infusions of ofatumumab (Cycle 1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 Days) in combination with up to 6 Cycles of intravenously infused bendamustine (70 mg/m2, Days 1 and 2, every 28 Days). The studies primary endpoint is overall response rate (ORR) as determined by Investigator evaluation. The ORR is the percentage of subjects achieving an objective response (i.e., partial response or better), using the IWCLL updated NCI-WG guidelines. Response assessments are planned at the following time-points: After 3 Cycles of ofatumumab plus bendamustine treatment, after 6 Cycles of ofatumumab plus bendamustine treatment and after the last dose, if not after 6 cycles, of ofatumumab plus bendamustine treatment. Follow-up assessments will be performed every 3 months following the last study treatment. The follow-up period will last for a maximum of 3 years. Response evaluation assessments to determine subject response or progression will be performed during the follow-up period, according to the IWCLL updated NCI-WG guidelines. Following progression, only survival status and details concerning the subject’s next CLL therapy will be recorded.

GSK Study ID:

115991


Has Results Document Available
ClinicalTrials.gov Identifier:

NCT01520922


EudraCT Number:

2011-005178-43


Study Overview

Medical Conditions

Leukaemia

Product

ofatumumab

Collaborators

N/A


Date

March 2012 to December 2015

Type

Interventional

Phase

1/2


Gender

Both

Age

18 Year+

Accepts Healthy Volunteers

none


Study Documents

This study has Protocol summary on ClinicalTrial.gov. Click here to learn more.

Locations

  • Central Contact :

    Not available

  • Central Contact Phone:

    877-379-3718

  • Central Contact Email:

    [email protected]


Study Design

  • Primary Purpose: Treatment
  • Allocation: N\A
  • Study Design: Single Group Assignment
  • Study Classification: Safety/Efficacy Study
  • Masking: Not Available
  • Masked Subject: No
  • Masked Caregiver: No
  • Masked Investigator: No
  • Masked Assessor: No
Primary Outcomes:

  • Number of participants with overall response (OR), as assessed by the investigator
    Timeframe: From the start of study treatment until 3 months after the last dose of study treatment

Secondary Outcomes:

  • Duration of response
    Timeframe: From time of initial response (CR, CRi, nPR, or PR) to disease progression or death, whichever came first (up to 3 years after the last doseof study treatment)

  • Number of participants with any adverse event (AE) or serious adverse event (SAE)
    Timeframe: From first dose of study medication to 60 days after the last dose of study medication (if the event is considered as an AE), or up to 3 years after the last dose of study treatment or until the time of the next anti-CLL therapy, if considered a SAE

  • Overall survival (OS)
    Timeframe: From the start of study treatment to the date of death due to any cause (up to 3 years after the last dose of study treatment)

  • Number of participants with the indicated cytogenetics testing at Baseline who also had a clinical response after last dose of study treatment
    Timeframe: From the start of study treatment until earliest date of disease progression or death (up to up to 3 months following last dose of study treatment)

  • Number of participants with confirmed positive response for human anti-human Antibodies (HAHA) at the indicated time points
    Timeframe: Cycle 1 Day 1 (C1D1), Cycle 6 Day 1 (C6D1), 6-Month Follow-up (F/U), and any post-dose time point

  • Change from Baseline in CD5-CD19+ cell counts at Screening, 3-Month Follow-up, and 6-Month Follow-up
    Timeframe: Screening, 3-Month Follow-up, and 6-Month Follow-up

  • Progression-free Survival (PFS)
    Timeframe: From the start of study treatment until earliest date of disease progression or death (up to 3 years after the last dose of study treatment)

  • Time to next therapy
    Timeframe: From the start of study treatment until the start of the next anti-CLL therapy (up to 3 years after the last dose of study treatment)

  • Number of participants with the indicated reduction in organomegaly (spleen and liver)
    Timeframe: Screening (Scr), Cycle 2 Day 1 (C2D1), Cycle 3 Day 1 (C3D1), Cycle 4 Day 1 (C4D1), Cycle 5 Day 1 (C5D1), Cycle 6 Day 1 (C6D1), 3-Month Follow-Up (F/U), 6-Month F/U and 9-Month F/U

  • Number of participants with the indicated constitutional or B-symptoms
    Timeframe: Screening (SCR), Cycle 1 Day 1 (C1D1), Cycle 2 Day 1 (C2D1) , Cycle 3 Day 1 (C3D1), Cycle 4 Day 1 (C4D1), Cycle 5 Day 1 (C5D1), Cycle 6 Day 1 (C6D1), 3-Month Follow-up (F/U), 6-Month F/U and 9-Month F/U

  • Number of participants who recived no transfusion or at least one transfusion during the study
    Timeframe: From start of treatment until earliest date of disease progression or death (up to 3 years after the last dose of study treatment)

  • Number of participants who were negative or positive for minimal residual disease (MRD) and achieved a bone marrow biopsy confirmed complete response (CR) at the 3-Month Follow-up
    Timeframe: From start of treatment until the 3-Month Follow-up visit

  • Number of participants with overall response (OR) with Computed Tomography (CT) Scan (CT scan) assessment, as assessed by the investigator
    Timeframe: From the start of study treatment until 3 months after the last dose of study treatment

  • Number of participants with the indicated Grade 3 or Grade 4 adverse event of infection
    Timeframe: From first dose of study medication to 60 days after the last dose of study medication (if the event is considered as an AE), or up to 3 years after the last dose of study treatment or until the time of the next anti-CLL therapy, if considered a SAE

  • Number of participants with complete response (CR) with and without a CT scan assessment after the last dose of study treatment, as assessed by the investigator
    Timeframe: From the start of study treatment until 3 months after the last dose of study treatment

  • Time to response
    Timeframe: From the start of study treatment to the first response (CR, CRi, nPR, or PR) (up to 3 Month Follow-up (F/U) visit)

  • Change from Baseline in cluster of differentiation (CD) CD5+CD19+ cell counts at Screening, 3-Month Follow-up, and 6-Month Follow-up
    Timeframe: Screening, 3-Month Follow-up, and 6-Month Follow-up

  • Number of participants with the indicated eastern cooperative oncology group (ECOG) performance status (PS)
    Timeframe: BL, Cycle 1 Day 1 (C1D1), Cycle 2 Day 1 (C2D1) , Cycle 3 Day 1 (C3D1), Cycle 4 Day 1 (C4D1), Cycle 5 Day 1 (C5D1), Cycle 6 Day 1 (C6D1), 3-Month F/U, 6-Month F/U and 9-Month F/U and last assessment (LA) at or prior to study treatment discontinuation

  • Number of participants with autoimmune hemolytic anaemia (AIHA) disease
    Timeframe: From first dose of study medication to 60 days after the last dose of study medication (if the event is considered as an AE), or up to 3 years after the last dose of study treatment or until the time of the next anti-CLL therapy, if considered a SAE

  • Number of participants with the indicated immunoglobulin heavy chain variable region (IgVH) testing at Baseline who also had a clinical response after last dose of study treatment
    Timeframe: From the start of study treatment until earliest date of disease progression or death (up to up to 3 months following last dose of study treatment)

  • Number of participants with the indicated Beta 2 microglobulin (B2M) at Baseline who also had a clinical response after the last dose of study treatment
    Timeframe: From the start of study treatment until earliest date of disease progression or death (up to up to 3 months following last dose of study treatment)

  • Mean change from Baseline in the Immunoglobulin (Ig) antibodies IgA, IgG, and IgM
    Timeframe: Baseline and last study visit/withdrawal visit (up to 3 years after the last dose of study treatment)

  • Number of participants with an adverse event of any infusion reactions (IR) or serious infusion reactions (SIR)
    Timeframe: From the first dose of study medication to 60 days after the last dose of study medication (up to 24 hours after last dose of study treatment)

  • Number of participants with zeta-chain-associated protein kinase (ZAP) 70 testing at Baseline who also had a clinical response after last dose of study treatment
    Timeframe: From the start of study treatment until earliest date of disease progression or death (up to 3 months following last dose of study treatment)

  • Number of participants with the indicated Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, and thrombocytopenia), as assessed by the investigator
    Timeframe: From the first dose of study medication to 60 days after the last dose of study medication

  • Time to progression
    Timeframe: From the start of study treatment to disease progression (up to 3 years after the last dose of study treatment)

  • Mean maximum decrease in sum of the product of the diameter (SPD) from Baseline in participants with lymphadenopathy at Baseline
    Timeframe: Baseline, Cycle 2 Day 1 (C2D1), Cycle 3 Day 1 (C3D1), Cycle 4 Day 1 (C4D1), Cycle 5 Day 1 (C5D1), Cycle 6 Day 1 (C6D1), 3-Month Follow-Up (F/U), 6-Month F/U and 9-Month F/U

Interventions:

  • drug: Bendamustine
  • vaccine: Ofatumumab
Inclusion / Exclusion Criteria: Click to view inclusion/exclusion criteria:
Enrollment: 99

Clinical Publications:

  • Ian W. Flinn, Offner, Panagiotidis, Afanasyev, Janssens, Grosicki, Homenda, Smolej, Kuliczkowski, Mayer, Domnikova. A Phase II, Multi-Center Study Investigating the Safety and Efficacy of Ofatumumab and Bendamustine Combination in Patients with Untreated or Relapsed Chronic Lymphocytic Leukemia (CLL). Am J Hematol.2016;91(9):900-6.