RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Total-body irradiation and drug therapy may be used to suppress the immune system and reduce the chance of developing graft-versus-host disease following transplantation. PURPOSE: Phase I/II trial to study the effectiveness of high-dose melphalan and autologous peripheral stem cell transplantation followed by immunosuppressive therapy and allogeneic peripheral stem cell transplantation in treating patients who have multiple myeloma.

Condition	Treatment or Intervention	Phase
stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma refractory plasma cell neoplasm	Drug: cyclophosphamide  Drug: cyclosporine  Drug: filgrastim  Drug: melphalan  Drug: mycophenolate mofetil  Drug: paclitaxel	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine engraftment of HLA identical peripheral blood stem cell allografts given after conditioning with total body irradiation and postgrafting immunosuppression with cyclosporine/mycophenolate mofetil in patients with multiple myeloma initially cytoreduced with high dose melphalan. II. Determine disease free survival of these patients at day 100 post allografting. III. Determine the efficacy of this regimen in terms of long term progression free survival of these patients.

PROTOCOL OUTLINE: Patients receive cyclophosphamide IV over 1-2 hours on day 1, paclitaxel IV over 4 hours on day 2, and filgrastim (G-CSF) subcutaneously (SQ) beginning on day 3 and continuing until the end of leukapheresis. Autologous peripheral blood stem cells (PBSC) are collected over 3-4 days and selected for CD34+ cells. Patients receive melphalan IV on day -2 (which is at least 31 days after paclitaxel), then autologous CD34+ PBSC are reinfused on day 0. G-CSF SQ or IV is administered beginning on day 0 and continuing until blood counts recover. About 40-120 days after autografting, patients receive cyclosporine IV twice a day on days -1 and 0, then orally on days 1-56 and oral mycophenolate mofetil twice a day on days 0-27. Patients undergo total body irradiation on day 0, followed by infusion of unmodified donor PBSC. At days 28 and 56, patients are evaluated for lymphoid and myeloid chimerism. Patients with stable mixed chimerism on day 56 without graft versus host disease receive nonmobilized donor lymphocyte infusion (DLI) over 30 minutes on day 65. Patients may receive up to 4 DLI's. Patients are followed weekly until day 90 after the last T-cell infusion, then at 4 and 6 months, then every 6 months for 1.5 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued within 4 years.

Ages Eligible for Study:  up to  65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Cytologically diagnosed multiple myeloma (MM) Stage II or III at diagnosis OR Progressive after initial diagnosis of stage I disease and received chemotherapy and/or radiotherapy
• Must have received at least 4 courses of conventional dose chemotherapy for MM
• HLA genotypically identical sibling available (not identical twin)

--Prior/Concurrent Therapy--

• Biologic therapy: No prior autograft
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics; No concurrent radiotherapy with melphalan administration
• Surgery: Not specified

--Patient Characteristics--

• Age: 65 and under
• Performance status: Karnofsky 60-100% (unless less than 60% due solely to MM)
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN); SGOT and SGPT no greater than 2 times ULN
• Renal: Creatinine clearance at least 40 mL/min
• Cardiovascular: LVEF at least 40%; No poorly controlled hypertension
• Pulmonary: DLCO at least 50% corrected; No continuous supplemental oxygen
• Other: Not pregnant; Fertile patients must use effective contraception during and for 12 months after study; HIV negative

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109,  United States

Study chairs or principal investigators

David G. Maloney,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000067153; FHCRC-1383.00; NCI-G99-1538
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003954
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08