A Phase II Trial of Ofatumumab (CALGB IND #) in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)
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.
- 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.
- 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.
18 Years and up
Accepting Healthy Volunteers?
- 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)
- 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
- 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