Chemotherapy, Radiation Therapy, Rituximab, and Umbilical Cord Blood Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma

OBJECTIVES:

Primary

• Determine the overall and event-free survival at 1 year in patients with B-cell lymphoid malignancies treated with a nonmyeloablative conditioning regimen, rituximab, and umbilical cord blood (UCB) transplantation (UCBT).

Secondary

• Determine the speed of neutrophil and platelet recovery post allograft in these patients.
• Determine the incidence and speed of donor-derived engraftment and contribution of each UCB unit to engraftment in these patients.
• Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days in these patients.
• Determine the incidence and severity of chronic GVHD at 1 year in these patients.
• Determine the incidence of serious infectious complications and correlate with laboratory measurements of immune recovery in these patients.
• Determine the response to vaccination after UCBT in these patients.
• Determine the incidence of treatment-related mortality at 100 days and 180 days in these patients.
• Determine the incidence of malignant relapse or disease progression at 1 and 2 years in these patients.
• Determine the probabilities of overall and event-free survival at 2 years after UCBT in these patients.
• Determine the performance of laboratory studies investigating double-unit biology and correlate with unit engraftment in these patients.

OUTLINE:

• Pre-transplant rituximab therapy: Patients receive rituximab IV on days -8 or -7 and on day -4.
• Nonmyeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV on day -6. Patients also undergo total-body irradiation on day -1.
• Umbilical cord blood transplantation: Patients undergo umbilical cord blood transplantation on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 7 and continuing until blood counts recover.
• Post-transplant rituximab therapy: Patients receive rituximab IV on days 7, 14, 21, and 28.
• Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2-4 hours or orally twice daily on days -3 to 100, followed by a taper. Patients also receive mycophenolate mofetil IV or orally three times daily on days -3 to 45, followed by a taper.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• CD20+* aggressive B-cell non-Hodgkin's lymphoma (NHL), including 1 of the following:

• Diffuse large cell (DLC) NHL meeting 1 of the following criteria:

• Relapsed disease after initial therapy but failed to mobilize or had bone marrow involvement and therefore is not suitable for an autologous stem cell transplantation
• High-intermediate or high-risk, second-line, age-adjusted International Prognostic Index (IPI) score and in second complete remission (CR) or partial remission (PR) after prior autologous stem cell transplantation
• Failed prior autologous stem cell transplantation and in at least PR after salvage chemotherapy
• Large cell transformation of indolent NHL/chronic lymphocytic leukemia (CLL) meeting the following criteria:

• CR/PR of the large cell component of disease after salvage chemotherapy or autologous stem cell transplantation
• Mantle cell lymphoma meeting 1 of the following criteria:

• High-risk, as defined by p53 positivity and in first CR/PR after initial therapy
• Relapsed disease after initial therapy and in second or third CR/PR after salvage chemotherapy
• CD20+* indolent NHL or CLL meeting the following criteria:

• Must be in second or subsequent progression (pre-allograft cytoreduction necessary but CR/PR not required)
• Indolent NHL includes, but is not limited to, any of the following:

• Follicular NHL
• Small cell NHL
• Marginal zone NHL NOTE: *CD20 positivity must be demonstrated within the past 12 months
• Relapsed disease must be biopsy proven
• Prior pre-allograft cytoreduction may have included 1 of the following:

• Single autologous stem cell transplantation with high-dose chemotherapy conditioning, if appropriate, and no conditioning prior to transplantation
• Two or more courses of intensive combination chemotherapy (e.g., rituximab, irinotecan hydrochloride, cetuximab, epirubicin hydrochloride [RICE]) as appropriate according to diagnosis and prior therapy

• Heavily pre-treated CLL patients in whom further combination chemotherapy is not appropriate may receive single-agent intermediate-dose cyclophosphamide for 2-3 courses
• No mantle cell or DLC NHL with progressive disease at allograft work-up
• No suitable matched related or unrelated donor available
• Two umbilical cord blood (UCB) units available meeting the following criteria:

• Units and recipient must be ≥ 4/6 HLA-A and -B antigen and DRB1 allele matched
• Each unit must have ≥ 1.5 x 10^7 total nucleated cells/recipient body weight

PATIENT CHARACTERISTICS:

• Karnofsky performance score 70-100%
• Creatinine clearance ≥ 50 mL/min
• Bilirubin < 2.5 mg/dL
• AST and ALT ≤ 3 times upper limit of normal (unless due to benign congenital hyperbilirubinemia)
• Spirometry and corrected DLCO ≥ 50% normal
• LVEF ≥ 40%
• Albumin ≥ 2.5 g/dL
• No active and uncontrolled infection at time of transplantation, including active infection with Aspergillus or other mold
• No HIV positivity
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No more than 120 days since prior autologous stem cell transplantation
• No more than 60 days since prior chemotherapy
• No prior allogeneic transplantation