Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma
Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
 so they stop growing or die. Peripheral stem cell transplantation may be able to replace
 immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells are
 rejected by the body's tissues. Peripheral stem cell transplantation with the person's own
 stem cells followed by donor peripheral stem cell transplantation may prevent this from
 happening.

 PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy with autologous
 peripheral stem cell transplantation and donor peripheral stem cell transplantation in
 treating patients who have multiple myeloma.
OBJECTIVES:

 -  Determine the incidence of early mortality in patients with multiple myeloma treated
 with melphalan and autologous peripheral blood stem cell (PBSC) transplantation followed
 by fludarabine, cyclophosphamide, and allogeneic PBSC transplantation.

 -  Determine the incidence of early allogeneic graft failure (before day 100 after
 allogeneic PBSC transplantation) and the incidence of severe acute graft-versus-host
 disease (GVHD) in patients treated with this regimen.

 -  Determine the toxicity of this regimen in these patients.

 -  Determine the overall and disease-free survival of patients treated with this regimen.

 -  Correlate changes in the T-cell population with clinical outcome, such as survival, in
 patients treated with this regimen.

 -  Correlate changes in the T-cell population with the incidence of GVHD, use of
 immunosuppressive agents, and effects of fludarabine in patients treated with this
 regimen.

 -  Determine the degree of chimerism after allogeneic PBSC transplantation and the time
 course over which it is established in patients treated with this regimen.

 OUTLINE: This is a multicenter study.

 Patients receive melphalan IV over 15 minutes on day -1. Autologous peripheral blood stem
 cells (PBSCs) are reinfused on day 0. Patients also receive sargramostim (GM-CSF)
 subcutaneously (SC) or IV over at least 30 minutes daily beginning on day 1 and continuing
 until blood counts recover. Beginning 100-182 days after autologous PBSC transplantation,
 patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over
 1-2 hours on days -3 and -2. Allogeneic PBSCs are infused on day 0. Patients may receive a
 second allogeneic PBSC infusion on day 1. Patients also receive GM-CSF SC or IV over at least
 30 minutes daily beginning on day 1 and continuing until blood counts recover. Cyclosporine
 is administered IV or orally twice daily as graft-versus-host disease (GVHD) prophylaxis,
 beginning on day -1 and continuing until day 60, followed by a taper in the absence of GVHD.

 Patients are followed for 5 years.

 PROJECTED ACCRUAL: A total 19-46 patients will be accrued for this study within 3 years.
DISEASE CHARACTERISTICS:

 -  Diagnosis of multiple myeloma meeting 1 of the following criteria:

 -  Bone marrow plasmacytosis with at least 10% plasma cells

 -  Sheets of plasma cells

 -  Biopsy-proven plasmacytoma

 -  Meets at least 1 of the following criteria:

 -  Presence of myeloma (M)-protein in the serum

 -  Presence of M-protein in the urine

 -  Radiographic evidence of osteolytic lesions

 -  Generalized osteoporosis allowed if at least 20% plasma cells in bone marrow

 -  No non-secretory myeloma

 -  Prior M-protein in serum or urine allowed provided patient is now in complete
 remission

 -  Must be receiving conventional-dose chemotherapy as initial therapy or as salvage
 therapy

 -  Must have HLA-A, -B, and -DR genotypically identical sibling donor

 PATIENT CHARACTERISTICS:

 Age:

 -  18 to 70

 Performance status:

 -  ECOG 0-2

 Life expectancy:

 -  Not specified

 Hematopoietic:

 -  See Disease Characteristics

 Hepatic:

 -  AST no greater than 3 times upper limit of normal

 -  Bilirubin less than 2.0 mg/dL

 Renal:

 -  Not specified

 Cardiovascular:

 -  LVEF greater than 40% at rest if symptomatic cardiac disease is present

 Pulmonary:

 -  DLCO greater than 50% of predicted (corrected for hemoglobin) if symptomatic pulmonary
 disease is present

 Other:

 -  Not pregnant or nursing

 -  Fertile patients must use effective contraception

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  No prior autologous or allogeneic peripheral blood stem cell or bone marrow
 transplantation

 Chemotherapy:

 -  See Disease Characteristics

 -  More than 28 days since prior chemotherapy (including primary chemotherapy for
 hematopoietic stem cell collection)

 -  No other concurrent cytotoxic chemotherapy between autologous and allogeneic
 transplantation

 Endocrine therapy:

 -  Prior dexamethasone or other corticosteroids allowed

 -  Concurrent corticosteroids between autologous and allogeneic transplantation allowed

 Radiotherapy:

 -  Concurrent radiotherapy between autologous and allogeneic transplantation allowed

 Surgery:

 -  Not specified