GM-CSF and Rituximab After Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Follicular Non-Hodgkin Lymphoma

OBJECTIVES:

Primary

• To assess the progression-free survival rate at 2 years after autologous stem cell transplantation (ASCT) in patients with relapsed or primary refractory follicular lymphoma treated with sargramostim (GM-CSF) and rituximab after ASCT.

Secondary

• To assess the safety of administering GM-CSF and rituximab after ASCT.
• To assess the effects of GM-CSF on the relative expression of activating and inhibitory FcγR on circulating monocytes.
• To assess the effects of GM-CSF on the relative expression of activating and inhibitory FcγR on circulating dendritic cells.
• To assess the effects of GM-CSF on the level of circulating FcγR.
• To assess the reconstitution of NK cells, NK-T cells, dendritic cell subsets, and regulatory T-cells after ASCT.

OUTLINE:

• High-dose chemotherapy: Patients receive carmustine IV over 2 hours on day -7, etoposide IV over 1 hour and cytarabine IV every 12 hours on days -6 to -3, and melphalan IV on day -2.
• Autologous stem cell transplantation (ASCT): Patients undergo ASCT on day 0. Patients receive filgrastim (G-CSF) subcutaneously (SC) once a day beginning on day 5 and continuing until blood counts recover.
• Sargramostim (GM-CSF) and rituximab: Beginning approximately 7-10 weeks (49-70 days) after ASCT, patients receive GM-CSF SC 3 times a week for 8 weeks and rituximab IV once weekly for 4 weeks (beginning within 3 days after the first dose of GM-CSF). Patients receive a second course of GM-CSF and rituximab (as above) beginning approximately 22-26 weeks (154-182 days) after ASCT.

After the completion of study treatment, patients are followed periodically for 2 years.

DISEASE CHARACTERISTICS:

• Histologic diagnosis of grade 1, 2, 3, or transformed follicular lymphoma
• Achieved a complete or partial response to last salvage therapy

• Completed salvage therapy within the past 12 weeks
• No disease progression since last salvage therapy
• One of the following disease statuses must have been present prior to receiving salvage therapy

• Refractory to last anti-lymphoma therapy
• Last remission duration less than 1½ years if salvage therapy is 3rd regimen
• Last remission duration less than 3 years if salvage therapy is 2nd regimen
• Minimum of 2 x 10^6 CD34+ cells/kg cryopreserved and available for hematopoietic stem cell support
• No leptomeningeal disease or brain parenchyma involvement

PATIENT CHARACTERISTICS:

• Cardiac ejection fraction > 50%

• If over 60 years of age, no evidence of cardiac ischemia by treadmill stress test (stress echo or sesta-MIBI)
• Adjusted diffusing capacity ≥ 50% of the predicted value on pulmonary function testing
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 50 mL/min
• ANC > 1,000/μL
• Platelet count > 50,000/μL
• Total bilirubin ≤ 2.0 mg/dL (≤ 3.0 mg/dL if Gilbert's disease is suspected)
• Not pregnant or breast-feeding
• Fertile patients must use an acceptable form of birth control
• HIV I or II negative
• No acute or chronic hepatitis B
• No active hepatitis C
• No medical illness (unrelated to non-Hodgkin lymphoma), including malignancies that, in the opinion of the attending physician and/or principal investigator, would preclude study treatment
• No other malignancy within the past 5 years except curatively treated cutaneous basal cell or squamous cell carcinoma or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

• No more than 3 prior anti-lymphoma regimens, inclusive of the salvage therapy

• Biologic agents (e.g., monoclonal antibodies and vaccines) administered as part of a planned treatment regimen will not be considered distinct regimens
• Chemotherapy administered primarily for the purpose of stem cell mobilization (e.g., cyclophosphamide at 2-4 g/m²) will not be considered an anti-lymphoma regimen
• No prior autologous or allogeneic hematopoietic stem cell transplantation