This phase II trial studies autologous peripheral blood stem cell transplant followed by donor bone marrow transplant in treating patients with high-risk Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic leukemia. Autologous stem cell transplantation uses the patient's stem cells and does not cause graft versus host disease (GVHD) and has a very low risk of death, while minimizing the number of cancer cells. Peripheral blood stem cell (PBSC) transplant uses stem cells from the patient or a donor and may be able to replace immune cells that were destroyed by chemotherapy. These donated stem cells may help destroy cancer cells. Bone marrow transplant known as a nonmyeloablative transplant uses stem cells from a haploidentical family donor. Autologous peripheral blood stem cell transplant followed by donor bone marrow transplant may work better in treating patients with high-risk Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic leukemia.
PRIMARY OBJECTIVES: I. Event-free survival (EFS) at 1-year after autograft. SECONDARY OBJECTIVES: I. Relapse rates at 1-year after autograft. II. Overall survival (OS) at 1-year after autograft. III. Incidence of grades II-IV acute GVHD and chronic extensive GVHD. IV. Non-relapse mortality (NRM) at 200 days and 1 year after allograft. V. Donor engraftment at day +84. VI. Incidence of infections. OUTLINE: CONDITIONING REGIMEN 1 (lymphoma, Waldenstrom macroglobulinemia, or chronic lymphocytic leukemia \[CLL\] with no dose limiting radiation or significant comorbidities: Patients receive cyclophosphamide intravenously (IV) on days -6 and -5. Patients undergo high-dose total body irradiation (TBI) twice daily (BID) on days -3 to -1. CONDITIONING REGIMEN 2 (lymphoma, Waldenstrom Macroglobulinemia, CLL, with prior dose-limiting radiation, or significant comorbidities): Patients receive carmustine IV on day -7, etoposide IV BID on days -6 to -3, cytarabine IV BID on days -6 to -3, and melphalan IV on day -2. CONDITIONING REGIMEN 3 (multiple myeloma or plasma cell leukemia, with no significant renal insufficiency or other significant comorbidities): Patients receive high-dose melphalan IV on day -2. CONDITIONING REGIMEN 4 (multiple myeloma or plasma cell leukemia, with significant renal insufficiency or other significant comorbidities): Patients receive lessened dose of melphalan IV on day -2. PBSC TRANSPLANTATION: All patients undergo autologous PBSC transplantation on day 0. WAITING INTERVAL: Between 40 and 120 days. NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV once daily (QD) on days -6 to -2 and cyclophosphamide IV QD on days -6 to -5 and day 3. Patients infused with donor's peripheral blood stem cells will additionally receive cyclophosphamide IV on day 4. Patients undergo low-dose TBI on day -1. ALLOGENEIC BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0. GRAFT VERSUS HOST DISEASE PROPHYLAXIS: Beginning on day 4, patients receive tacrolimus orally (PO) or IV and taper beginning on day 86 if no graft-versus-host disease. Patients also receive mycophenolate mofetil PO thrice daily (TID) on days 4 - 35. PERIPHERAL BLOOD COUNT SUPPORT: Patients receive filgrastim (G-CSF) IV or subcutaneously (SC) beginning from day 4 and continue till blood counts recover. ALLOGENEIC PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) TRANSPLANTATION: Patients undergo donor PBMC transplantation on day 0. GRAFT VERSUS HOST DISEASE PROPHYLAXIS: Beginning on day 5, patients receive tacrolimus orally (PO) or IV and taper beginning on day 86 if no graft-versus-host disease. Patients also receive mycophenolate mofetil PO thrice daily (TID) on days 5 - 35. PERIPHERAL BLOOD COUNT SUPPORT: Patients receive filgrastim IV or SC beginning from day 5 and continue till blood counts recover. After completion of study treatment, patients are followed up annually for 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Undergo donor HCT
Undergo donor HCT
Undergo autologous PBSC transplant
Undergo autologous-donor tandem HCT
Given IV
Given IV
Given IV
Given IV
Given IV
Correlative study
Given IV
Given PO
Undergo donor HCT
Given IV or PO
Undergo TBI
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Event-Free Survival (EFS)
Number of patients surviving without relapsed/progressive disease
Time frame: 1 Year post-autograft
Number of Patients With Relapsed/Progressive Disease
Relapse/Progression defined as: Nodes, liver, and/or spleen ≥50% increased or new by physical exam / imaging studies. Circulating lymphocytes ≥50% increased by morphology and/or flow cytometry. Richter's transformation by lymph node biopsy .
Time frame: 1 year post-autograft
Overall Survival
Number of patients surviving one year post-autograft
Time frame: 1 year post-autograft
Number of Patients With Grade II-IV Acute Graft-versus-Host-Disease and/or Chronic Extensive Graft-versus-Host-Disease
aGVHD The diagnosis of aGVHD is identified through various stages and grading of the disease related to Skin (Rash), Gut (Diarrhea, Nausea/vomiting and/or anorexia) and the liver (Bilirubin) assessed by severity and grading scale outlined in the section Grafts vs Hosts by Sullivan (1999). GVHD Grades Grade I: 1-2 Skin Rash; No gut or liver involvement Grade II: Stage 1-3 Skin rash; Stage 1 gut and/or stage 1 liver involvement Grade III: Stage 2-4 gut involvement and/or stage 2-4 liver involvement with or without rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death CGVHD The diagnosis of cGVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.
Time frame: 1 year post-allograft,
Non-relapse Mortality (NRM)
Number of patients with non-relapse mortalities.
Time frame: 200 days and 1 Year post-allograft
Number of Patients Who Engrafted
Number of patients with donor engraftment.
Time frame: Day 84 post-allograft
Number of Patients Who Had Infections
Number of patients who had infections.
Time frame: 1 Year post-autograft
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