Melphalan and Busulfan Followed By Donor Peripheral Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Multiple Myeloma

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00313625

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy, such as melphalan and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus and methotrexate before or after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving melphalan together with busulfan followed by donor peripheral stem cell transplant, tacrolimus, and methotrexate works in treating patients with multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: busulfan Drug: melphalan Drug: methotrexate Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES:

Primary

Evaluate transplant-related mortality in patients with multiple myeloma treated with a myeloablative conditioning regimen comprising melphalan and busulfan followed by HLA-matched, allogeneic peripheral blood stem cell transplantation (PBSCT) and graft-vs-host disease prophylaxis with tacrolimus and methotrexate.

Secondary

Determine the disease response in patients treated with this regimen.
Determine the 1-year progression-free survival and overall survival in patients treated with this regimen.

OUTLINE:

Conditioning regimen: Patients receive melphalan IV over 30 minutes on day -6 and busulfan IV over 3 hours on days -5 to -3.
Peripheral blood stem cell transplantation (PBSCT): Patients undergo HLA-matched, related donor, allogeneic PBSCT on day 0.
Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -2 and continuing until day 80 followed by a taper until day 180 in the absence of GVHD or disease progression. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Intravenous Melphalan and Busulfan Followed by HLA-Matched, Allogeneic Peripheral Blood Stem Cell Transplant for the Treatment of Multiple Myeloma

Study Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Jul 1, 2007

Outcome Measures

Primary Outcome Measures

Transplant-related mortality at 180 days []

Secondary Outcome Measures

Disease response (complete response) []
Progression-free survival []
Overall survival at 1 year []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of multiple myeloma
Stage I disease with disease progression during the second of ≥ 2 lines of prior therapy
Stage II or III disease, meeting 1 of the following criteria:
Failed to achieve at least a partial response after ≥ 2 courses of prior therapy
Progressive disease after ≥ 2 courses of prior therapy
Presented with high-risk features at diagnosis, including any of the following:
Cytogenetic abnormality
Del 13 or 4,14 by fluorescent in situ hybridization (FISH)
Elevated lactic dehydrogenase
Beta 2 microglobulin > 5.5
Circulating peripheral blood plasma cells
Any stage disease with disease progression > 6 months after prior autologous stem cell transplantation
Availability of an HLA-matched, related donor between 12 and 75 years of age*
No bone marrow donors NOTE: *Donors > 75 years of age are eligible at the discretion of the principal investigator