Rituximab and Galiximab in Treating Patients With Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma

A Phase II Trial of Extended Induction Galiximab (Anti-CD80 Monoclonal Antibody) (IND #12373) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL)

RATIONALE: Monoclonal antibodies, such as rituximab and galiximab, 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. Giving more than one monoclonal antibody may be a better way to block cancer growth.

PURPOSE: This phase II trial is studying how well giving rituximab together with galiximab works in treating patients with stage II, stage III, or stage IV non-Hodgkin's lymphoma.

OBJECTIVES:

Primary

• Determine the overall and complete response rate in patients with previously untreated CD20-positive bulky stage II or stage III or IV follicular non-Hodgkin's lymphoma treated with rituximab and galiximab.
• Determine the time to disease progression in patients treated with this regimen.

Secondary

• Determine the toxicity profile of this regimen in these patients.
• Correlate Fc receptor polymorphism profiling with response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Induction therapy (month 1): Patients receive rituximab IV on days 1, 8, 15, and 22 and galiximab IV over 1 hour on day 3, 8, 15, and 22.
• Extended induction therapy (months 3, 5, 7, and 9): Beginning in month 3, patients receive rituximab and galiximab as above on day 1. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 4 months for up to 10 years.

PROJECTED ACCRUAL: A total of 51 patients will be accrued for this study within 18 months.

1. Documentation of Disease

   1.1 Previously untreated, histologically confirmed follicular lymphoma, WHO classification, grade 1, 2, or 3a (> 15 centroblasts per high power field with centrocytes present) which is stage III, IV, or bulky (i.e., single mass ≥ 7 cm in any unidimensional measurement) stage II.

   1.1.1 Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies. Fine needle aspirates are not acceptable.

   1.1.2 Failure to submit pathology specimens within 60 days of patient registration will result in the patient being declared ineligible.

   1.2 Institutional flow cytometry or immunohistochemistry must confirm CD20 antigen expression.

   1.3 Patients classified as high risk according to the Follicular Lymphoma International Prognostic Index (FLIPI) should be considered for CALGB 50102/SWOG S0016 (A Phase III Trial of CHOP vs CHOP + Rituximab vs CHOP + Iodine-131-Labeled Monoclonal Anti-B1 Antibody [Tositumomab] For Treatment of Newly Diagnosed Follicular Non-Hodgkin's Lymphomas).

2. Prior Treatment

   2.1 No prior therapy for non-Hodgkin lymphoma including chemotherapy, radiation or immunotherapy (e.g., monoclonal antibody-based therapy)

   2.2 No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease

3. Age - Patients must be ≥ 18 years of age

4. ECOG Performance Status - Patients must have ECOG Performance Status 0-2.

5. Measurable Disease - Measurable disease must be present either on physical examination or imaging studies.

   5.1 Non-measurable disease alone is not acceptable.

   5.2 Any tumor mass > 1 cm is acceptable.

   5.3 Lesions that are considered non-measurable include the following:

   • Bone lesions (lesions if present should be noted)
   • Ascites
   • Pleural/pericardial effusion
   • Lymphangitis cutis/pulmonis
   • Bone marrow (involvement by non-Hodgkin lymphoma should be noted).

6. CNS Involvement - Patients must have no known CNS involvement by lymphoma.

7. HIV Infection - Patients must have no known HIV infection.

   7.1 Patients with a history of intravenous drug abuse or any behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus.

   7.2 Patients who test positive or who are known to be infected are not eligible due to an increased risk of infection with this regimen. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk.

8. Human Anti-Chimeric Antibody - Patients must have no known baseline human anti-chimeric antibody (HACA) positivity.

9. Pregnancy and Nursing Status - Patients must be non-pregnant and non-nursing.

   9.1 Due to the unknown teratogenic potential of galiximab, pregnant or nursing patients may not be enrolled.

   9.2 Women and men of reproductive potential should agree to use an effective means of birth control throughout their participation in this study.

   9.3 Appropriate methods of birth control include oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom).

10. Second Malignancy - Patients with a "currently active" second malignancy, other than non-melanoma skin cancers are not eligible.

    10.1 This includes Waldenstrom's Macroglobulinemia, since such patients have experienced transient increases in IgM following initiation of rituximab, with the potential for hyperviscosity syndrome requiring plasmapheresis.

    10.2 Patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse.

11. Required Initial Laboratory Values:

    • ANC ≥ 1000/µL
    • Platelet Count ≥ 50,000/µL
    • Creatinine ≤ 2 x ULN Unless attributable to lymphoma
    • Total Bilirubin ≤ 2 x ULN*† Unless attributable to Gilbert's disease