RATIONALE: Stem cell transplantation may be able to replace immune cells that were destroyed by previous cancer treatment. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Cyclosporine and mycophenolate mofetil may prevent this from happening.

PURPOSE: Phase I/II trial to study the effectiveness of donor stem cell transplantation in treating patients who have multiple myeloma that has been previously treated.

Condition	Treatment or Intervention	Phase
stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma refractory plasma cell neoplasm	Drug: allogeneic lymphocytes  Drug: cyclosporine  Drug: fludarabine  Drug: melphalan  Drug: mycophenolate mofetil  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: graft versus tumor induction  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase I Phase II

OBJECTIVES:

• Determine the efficacy of allogeneic hematopoietic stem cell transplantation, in terms of 1-year progression-free survival and overall survival, in patients with previously treated multiple myeloma.
• Determine non-relapse mortality at day 100 in patients treated with this regimen.
• Determine the incidence of grade II-IV acute graft-versus-host disease (GVHD) and chronic extensive GVHD in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive fludarabine IV on days -5 to -3 and melphalan IV over 15-20 minutes on day -2. Patients undergo total body irradiation and allogeneic hematopoietic stem cell transplantation on day 0.

Patients also receive graft-versus-host disease prophylaxis according to the type of donor.

• Related donor: Patients receive oral cyclosporine every 12 hours on days -3 to 80 followed by a taper until day 180 and oral mycophenolate mofetil every 12 hours on days 0-27.
• Unrelated donor: Patients receive oral cyclosporine every 12 hours on days -3 to 100 followed by a taper until day 177 and oral mycophenolate mofetil every 8 hours on days 0-40 followed by a taper until day 96. Patients are followed at days 28, 56, and 84; at months 6, 12, 18, and 24; and then annually for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma, meeting 1 of the following criteria:
• Progressive disease after 1 prior autologous hematopoietic stem cell transplantation (HSCT) (indicated by greater than 25% increase in serum or urine paraprotein levels or appearance of new lytic bone lesions or plasmacytomas)
• Unable to collect autologous peripheral blood stem cells due to poor marrow reserve and has progressive disease after at least 4 prior courses of standard chemotherapy (e.g., dexamethasone/doxorubicin/vincristine)
• Availability of 1 of the following donors:
• HLA genotypically matched identical sibling
• HLA phenotypically matched relative
• HLA phenotypically matched unrelated donor
• Matched for serologically recognized HLA-A or B or C antigens and at least 5/6 HLA-A or B or C alleles
• Matched for HLA-DRB1 and DQB1 alleles
• No identical twins

PATIENT CHARACTERISTICS: Age

• 18 to 70

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• SGPT and SGOT no greater than 4 times ULN

Renal

• Creatinine clearance at least 40 mL/min

Cardiovascular

• LVEF at least 40%
• No symptomatic heart failure
• No poorly controlled hypertension

Pulmonary

• DLCO at least 50%
• No requirement for continuous supplemental oxygen

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after study participation
• HIV negative
• Cytomegalovirus (CMV)-antigenemia negative
• No impaired capacity that would preclude informed consent
• No persistent mucositis or gastrointestinal symptoms requiring hyperalimentation and/or IV hydration

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Disease Characteristics
• No concurrent thalidomide

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• No concurrent steroids for autologous graft-versus-host disease

Radiotherapy

• No other concurrent radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• At least 2 weeks since prior ganciclovir or foscarnet for previous CMV reactivation/infection
• No concurrent ganciclovir or foscarnet for previous CMV reactivation/infection
• No concurrent IV antibiotics for active infections
• No concurrent bisphosphonates during and for 30 days after transplantation

Texas
      Texas Oncology, P.A. at Charles A. Sammons Cancer Center, Dallas,  Texas,  75246,  United States; Recruiting
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States; Recruiting
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting

Study chairs or principal investigators

Marco B. Mielcarek, MD,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000270417; FHCRC-1743.00
Record last reviewed:  March 2004
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00054353
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-18