Single Agent Ofatumumab Vs. Single Agent Rituximab in Follicular Lymphoma Relapsed After Rituximab-Containing Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01200589
First received: September 10, 2010
Last updated: July 3, 2014
Last verified: June 2014
  Purpose

This is a multi-center, parallel, active comparator controlled, open-label, randomized (1:1) phase III study of single agent ofatumumab compared to single agent rituximab in subjects with rituximab-sensitive grade 1, 2, and 3A follicular lymphoma that has relapsed at least 6 months after completing treatment with single agent rituximab or a rituximab-containing regimen. Subjects must have attained a Complete Response or Partial Response to their last prior rituximab containing therapy lasting at least six months beyond the end of rituximab therapy. Subjects will receive four weekly doses of single agent ofatumumab (1000 mg) or rituximab (375 mg/m2), followed by ofatumumab (1000 mg) or rituximab (375 mg/m2) every 2 months for four additional doses. Therefore, subjects will receive a total of eight doses of anti-CD20 antibody over 9 months. Subjects will be evaluated for response after completion of the first four doses of therapy, after six doses of therapy, and after completion of study therapy. Subjects will be followed until the end of the designated follow-up period (total study duration of 200 weeks) or until they meet the withdrawal criteria.


Condition Intervention Phase
Lymphoma, Follicular
Biological: Ofatumumab
Biological: Rituximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Randomized, Open Label Study of Single Agent Ofatumumab Vs. Single Agent Rituximab in Follicular Lymphoma Relapsed After Rituximab-Containing Therapy

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 200 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • complete response rate [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
  • overall response rate [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
  • duration of response [ Time Frame: 200 weeks ] [ Designated as safety issue: No ]
  • time to next treatment [ Time Frame: 200 weeks ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: 200 weeks ] [ Designated as safety issue: Yes ]
  • infectious toxicity [ Time Frame: 44 weeks ] [ Designated as safety issue: Yes ]
  • pharmacokinetics [ Time Frame: 70 weeks ] [ Designated as safety issue: No ]
  • infusion related events [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
  • hematological toxicity [ Time Frame: 44 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 516
Study Start Date: October 2010
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Ofatumumab Biological: Ofatumumab
Four weekly doses of single agent ofatumumab (1000 mg), followed by ofatumumab (1000 mg) every two months for four additional doses.
Other Name: Arzerra
Active Comparator: Arm B: Rituximab Biological: Rituximab
Four weekly doses of single agent rituximab (375 mg/m2), followed by rituximab (375 mg/m2) every two months for four additional doses.
Other Names:
  • Mabthera
  • Rituxan

  Eligibility

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

Inclusion Criteria:

  1. Follicular lymphoma (FL); grades 1, 2 and 3A, defined according to World Health Organization guidelines.
  2. Rituximab-sensitive FL, defined as a partial or complete response to treatment with rituximab or a rituximab-containing regimen lasting at least 6 months following completion of the last rituximab treatment.
  3. Relapse or disease progression following response to prior rituximab-based therapy, as defined by 2007 Revised Response Criteria for Malignant Lymphoma criteria, which requires therapy.
  4. Radiographically measurable disease, defined as at least one clearly demarcated lesion with a largest diameter ≥ 2.0 cm by CT scan imaging.
  5. ECOG Performance Status of 0, 1, or 2.
  6. Age ≥ 18 years.
  7. Life expectancy of at least 6 months in the opinion of the investigator.
  8. The patient or their legally acceptable representative must be capable of giving written informed consent prior to performing any study-specific tests or procedures.
  9. All prior treatment related non-hematologic toxicities (with the exception of alopecia) must have resolved to CTCAE (Version 4.0) ≤ Grade 2 at the time of randomization.

French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

  1. Previous treatment with ofatumumab.
  2. Previous radioimmunotherapy (RIT) within 6 months of randomization. Patients who have received previous RIT must have attained a partial or complete response lasting at least 6 months, and must have recovered from any hematologic or other toxicity.
  3. Previous autologous stem cell transplantation within 6 months of randomization.
  4. Previous allogeneic stem cell transplantation.
  5. Previous anti-lymphoma monoclonal antibody therapy (excluding rituximab), chemotherapy, glucocorticoid, or other systemic therapy for lymphoma within 3 months of randomization.
  6. Current or previous participation in another interventional clinical study within 4 weeks of randomization.
  7. Current or previous other malignancy within 2 years of randomization. Subjects who have been free of malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer or successfully treated carcinoma in situ, are eligible.
  8. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis C, and known HIV disease.
  9. Clinically significant cardiac disease as judged by the investigator including unstable angina, acute myocardial infarction within 6 months of randomization, congestive heart failure, and arrhythmia requiring therapy.
  10. Other significant concurrent, uncontrolled medical conditions including, but not limited to, renal, hepatic, autoimmune, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which, in the investigator's opinion, will impact study participation.
  11. Screening laboratory values:

    1. Neutrophils < 1.5 x 109/L (unless due to FL involvement of the bone marrow).
    2. Platelets < 50 x 109/L (unless due to FL involvement of the bone marrow).
    3. ALT or AST > 2xULN, alkaline phosphatase and bilirubin > 1.5xULN (isolated predominantly indirect hyperbilirubinemia due to Gilbert's syndrome is acceptable for inclusion)
  12. Known or suspected inability to fully comply with study protocol

a. Lactating women. b. Women with a positive pregnancy test at study entry c. Men with partners of childbearing potential and women of childbearing potential who are not willing to use adequate contraception from study entry through one year following last treatment dose.

14. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones).

15. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01200589

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

  Show 155 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01200589     History of Changes
Other Study ID Numbers: 113676
Study First Received: September 10, 2010
Last Updated: July 3, 2014
Health Authority: Slovakia: State Institute for Drug Control
France: Conseil National de l'Ordre des Médecins
Bulgaria: The Bulgarian Drug Agency
Pakistan: Drug Controller R&D Ministry of Health
Hungary: National Institute of Pharmacy
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Japan: Pharmaceutical and Medical Device Agency
Canada: Biologics and Genetic Therapies Directorate (BGTD)
Brazil: ANVISA
Ukraine: State Pharmacological Center of Ministry of Health of Ukraine
United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control

Keywords provided by GlaxoSmithKline:
Follicular Lymphoma
Randomized trial
Ofatumumab
Rituximab

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 23, 2014