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

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00313625
• Other study ID #: 2018.00
• Secondary ID: FHCRC-2018.00CDR
• Status: Completed
• Phase: Phase 2
• First received: April 11, 2006
• Last updated: September 20, 2010
• Start date: September 2005

Study information

• Verified date: September 2010
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%

• Creatinine clearance > 60 mL/min

• Bilirubin = 2.5 mg/dL

• ALT/AST < 2 times upper limit of normal

• Cardiac ejection fraction = 49%

• DLCO = 50% corrected

• FEV_1 = 60%

• Not pregnant or nursing

• Fertile patients must use effective contraception

• HIV negative

• No cirrhosis

• No chronic inflammatory or fibrotic liver disease

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 6 months since prior autologous transplantation

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Drug:
• busulfan

• melphalan

• methotrexate

• tacrolimus

Procedure:
• allogeneic hematopoietic stem cell transplantation

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Transplant-related mortality at 180 days			No
Secondary	Disease response (complete response)			No
Secondary	Progression-free survival			No
Secondary	Overall survival at 1 year			No