Ofatumumab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01190449
First received: August 26, 2010
Last updated: February 15, 2013
Last verified: February 2013
  Purpose

RATIONALE: Monoclonal antibodies, such as ofatumumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.

PURPOSE: This randomized phase II trial is studying ofatumumab to see how well it works in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma
Biological: ofatumumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Ofatumumab (CALGB IND #) in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall response (complete or partial response) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]
  • Tolerability [ Designated as safety issue: Yes ]
  • Comparison of two ofatumumab doses efficacy with historical controls [ Designated as safety issue: No ]
  • Comparison of two ofatumumab doses toxicity with historical controls [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: August 2011
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive high-dose ofatumumab IV over 2-8 hours on days 1, 8, 15, and 22 and then once monthly in months 3-9.
Biological: ofatumumab
Given IV
Experimental: Arm II
Patients receive a lower dose of ofatumumab IV over 2-8 hours on days 1, 8, 15, and 22 and then once monthly in months 3-9.
Biological: ofatumumab
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • To determine the response rate in patients with previously untreated CD20-positive bulky stage II, or stage III or IV follicular non-Hodgkin lymphoma (NHL) treated with a lower- or high-dose of ofatumumab.

Secondary

  • To determine the progression-free survival (PFS) of patients treated with these regimens.
  • To determine the toxicity profile of these regimens in these patients.
  • To establish whether the therapeutic effect of single-agent ofatumumab is sufficiently promising to warrant evaluation in subsequent randomized, ofatumumab-based, biologic doublet trials.
  • To evaluate the two ofatumumab doses by independent comparison of response, PFS, and toxicity to a historical control in previously untreated patients with follicular NHL.
  • To prospectively validate the FLIPI2 prognostic index in low- and intermediate-risk patients and compare to low- and intermediate-risk stratified patients by standard FLIPI scoring to determine a more reliable indicator of response and PFS.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive high-dose ofatumumab IV over 2-8 hours on days 1, 8, 15, and 22 and then once monthly in months 3-9.
  • Arm II: Patients receive a lower dose of ofatumumab IV over 2-8 hours on days 1, 8, 15, and 22 and then once monthly in months 3-9.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood and bone marrow sample collection for correlative studies.

After completion of study therapy, patients are followed up every 4 months for 2 years and then every 6 months for 8 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed follicular non-Hodgkin lymphoma (NHL) meeting 1 of the following criteria:

    • Bulky (i.e., single mass ≥ 7cm in any uni-dimensional measurement) stage II disease
    • Stage III or IV disease
  • WHO grade 1, 2, or 3a disease
  • Bone marrow biopsies allowed provided they are submitted in conjunction with nodal biopsies

    • No fine-needle aspirates for diagnosis
  • Tumor tissue must express the CD20-positive antigen by flow cytometry or IHC
  • At least 1 site of measurable disease that is > 1 cm in diameter in ≥ 1 dimension present either on physical exam or imaging studies

    • Non-measurable disease alone not allowed, including the following:

      • Bone lesions (lesions if present should be noted)
      • Ascites
      • Pleural/pericardial effusion
      • Lymphangitis cutis/pulmonis
      • Bone marrow (involvement by NHL should be noted)
  • Low- or intermediate-risk disease by the Follicular Lymphoma International Prognostic Index (FLIPI)

    • FLIPI score meeting 1 or 2 of the following risk factors:

      • Age > 60 years
      • Involvement of > 4 nodal sites
      • Stage III-IV disease
      • Hemoglobin < 12.0 g/dL
      • LDH normal
    • Risk determined by the following:

      • Low Risk: 0-1 of the above risk factors
      • Intermediate Risk: 2 risk factors
      • Poor Risk: ≥ 3 risk factors
  • No known CNS involvement

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • ANC ≥ 1,000/μL
  • Platelet count ≥ 75,000/μL
  • Creatinine clearance ≥ 30 mL/min
  • Bilirubin ≤ 2 times upper limit of normal (unless secondary to Gilbert syndrome or hepatic involvement of NHL)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • Patients with HIV infection allowed provided the following criteria are met:

    • No evidence of coinfection with hepatitis B or C
    • CD4+ cell count ≥ 400/mm³
    • No evidence of resistant strains of HIV
    • HIV viral load < 10,000 copies HIV RNA/mL if not on anti-HIV therapy OR HIV viral load < 50 copies if on anti-HIV therapy
    • No history of AIDS-defining conditions
  • No evidence of active hepatitis B (HBV) or C (HCV) infection (i.e., no positive serology for anti-HBc or anti-HCV antibodies)

    • HBV seropositivity allowed (HBsAg+) provided they are closely monitored for evidence of active HBV infection by HBV DNA testing
    • After completing treatment, HBsAg + patients must be monitored by HBV DNA testing every 2 months for 6 months post-treatment, while continuing lamivudine (required)

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy) for NHL

    • Prior involved-field radiation therapy allowed
  • More than 2 weeks since prior corticosteroids except for maintenance therapy for a non-malignant disease

    • No concurrent dexamethasone or other steroids as antiemetics
  • No live virus vaccination within 6 weeks prior to study entry
  • No concurrent zidvoudine or stavudine
  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: NCT01190449

  Show 48 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Principal Investigator: Cara A. Rosenbaum, MD University of Chicago
  More Information

Additional Information:
No publications provided

Responsible Party: Richard L. Schilsky, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT01190449     History of Changes
Other Study ID Numbers: CDR0000683083, CALGB-50901, GSK-CALGB-50901
Study First Received: August 26, 2010
Last Updated: February 15, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 22, 2014