Ofatumumab and Bendamustine Combination Therapy Compared With Bendamustine Monotherapy in Indolent B-cell Non-Hodgkin's Lymphoma (NHL) Unresponsive to Rituximab or a Rituximab-Containing Regimen (COMPLEMENT A+B)

This study is currently recruiting participants.
Verified March 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01077518
First received: February 25, 2010
Last updated: April 10, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate the safety and efficacy of ofatumumab and bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.


Condition Intervention Phase
Lymphoma, Follicular
Drug: Ofatumumab and Bendamustine infusions (Arm A)
Drug: Bendamustine infusion (Arm B)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open Label Study of Ofatumumab and Bendamustine Combination Therapy Compared With Bendamustine Monotherapy in Indolent B-cell Non-Hodgkin's Lymphoma Unresponsive to Rituximab or a Rituximab-Containing Regimen During or Within Six Months of Treatment

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Progression-free-survival following ofatumumab and bendamustine combination therapy [ Time Frame: 68 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical benefit, changes in patient reported outcome measures, and pharmacokinetics following ofatumumab and bendamustine combination therapy [ Time Frame: 62 months ] [ Designated as safety issue: No ]
  • Overall response rate, overall survival, time to and duration of response following ofatumumab and bendamustine combination therapy [ Time Frame: 62 months ] [ Designated as safety issue: No ]
  • Safety and tolerability of ofatumumab and bendamustine combination therapy [ Time Frame: 62 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 346
Study Start Date: August 2010
Estimated Study Completion Date: May 2022
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab and Bendamustine (Arm A)
Up to 8 cycles of bendamustine (90 mg/m2) on Days 1,2 every 21 days with12 doses of ofatumumab (1000 mg, Day 1 q21 days when with bendamustine and q28 days when given as monotherapy)
Drug: Ofatumumab and Bendamustine infusions (Arm A)
Up to 8 cycles of Bendamustine (90 mg/m2 Days 1 and 2, every 21 days) given in combination with 12 doses of ofatumumab (1000 mg). Ofatumumab will be given on day 1 of each cycle of bendamustine as long as patients in Arm A receive bendamustine. Once patients in Arm A complete bendamustine therapy, the remaining doses of ofatumumab will be given monthly until all 12 doses are completed.
Active Comparator: Bendamustine (Arm B)
Up o 8 cycles of bendamustine (120 mg/m2) on Days 1,2 every 21 days
Drug: Bendamustine infusion (Arm B)
Bendamustine (120 mg/m2 Days 1 and 2, every 21 days, up to 8 cycles).

Detailed Description:

Ofatumumab is an anti-CD20 monoclonal antibody shown to have monotherapy activity in patients with follicular lymphoma that has relapsed following rituximab-containing therapy. Bendamustine was approved by FDA for the treatment of in patients with indolent B-cell Non-Hodgkin's Lymphoma (NHL) that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Biologics have demonstrated enhanced efficacy when added to chemotherapeutic combinations in the frontline treatment for indolent NHL. The combination of ofatumumab and bendamustine may provide additional clinical benefit and efficacy to those who no longer respond to rituximab or rituximab-containing regimens.

The objective of this study is to determine the effect of ofatumumab and bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Indolent lymphoma including Grades 1-3a follicular, small lymphocytic, lymphoplasmacytic, and marginal zone lymphoma; Stages III-IV, or bulky disease, Stage II. Tumor verified CD20+ and CT imaging done at screening verifying disease
  • Indolent B-cell NHL that remains stable or unresponsive during or within 6 months of treatment with rituximab or a rituximab-containing regimen
  • Indolent lymphoma including grades 1-3a follicular, small lymphocytic, lymphoplasmacytic, and marginal zone lymphoma; stages III-IV, or bulky disease stage II (i.e. as any single mass > 5 cm in any direction)
  • ECOG Performance Status of 0, 1, or 2
  • Life expectancy of at least 6 months
  • 18 years or older
  • Signed, written informed consent

Exclusion Criteria:

  • Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma
  • Previous allogeneic stem cell transplant
  • Previous autologous stem cell transplant, fludarabine therapy, or radioimmunotherapy in the past 12 months
  • Previous external beam radiation therapy to the pelvis. Previous external beam radiation therapy for bony disease to the cranium, mediastinum, and axilla, or to two or to more than 3 vertebral bodies
  • High dose steroids greater to or equal to 60 mg prednisone/day (or equivalent) within 3 months of randomization. No more than 10 mg prednisone (or equivalent) daily at the time of randomization
  • Prior bendamustine treatment within 1 year of randomization not resulting in a CR or PR for at least 6 months
  • Treatment with anti-CD20 monoclonal antibody within 3 months of randomization
  • Known CNS involvement of indolent lymphoma
  • Other past or current malignancy. Subjects free of malignancy for at least 5 years or have history of definitively treated non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible
  • Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
  • Clinically significant cardiac disease
  • History of significant cerebrovascular disease or event with significant symptoms
  • Positive serology for Hepatitis B
  • Current active liver or biliary disease (except Gibler's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease)
  • Known HIV positive
  • Abnormal/inadequate blood values, liver and kidney function
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01077518

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 136 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01077518     History of Changes
Other Study ID Numbers: 110918
Study First Received: February 25, 2010
Last Updated: April 10, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Refractory
Safety
Efficacy
Rituximab refractory
Oncology

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Rituximab
Nitrogen Mustard Compounds
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 16, 2014