Fludarabine, Busulfan, Antithymocyte Globulin, and Donor Stem Cell Transplant in Treating Patients With Multiple Myeloma That Has Not Responded to Treatment

Study Overview
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Brief Summary
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RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). PURPOSE: This phase II trial is studying the side effects of giving fludarabine together with busulfan and antithymocyte globulin followed by donor stem cell transplant and to see how well it works in treating patients with multiple myeloma that has not responded to treatment.

Detailed Description
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OBJECTIVES: Primary To study the toxicity of reduced intensity conditioning comprising fludarabine phosphate, busulfan, and anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation in patients with refractory or relapsed multiple myeloma. Secondary To study the tumor response in these patients. To study the incidence of acute or chronic graft-versus-host disease in these patients. To study the incidence of infectious complications in these patients. To study relapse- or progression-free and overall survival of these patients. To study the biological mechanisms (i.e., taking graft, immunological recovery, antitumor activity, and chimerism). OUTLINE: This is a multicenter study. Patients receive reduced intensity conditioning comprising fludarabine IV on days -5 to -1, oral busulfan on days -4 and -3, and anti-thymocyte globulin IV on days -2 and -1. Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. After completion of study therapy, patients are followed every month for 6 months and then every 3 months for 1½ years.

Official Title
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Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation Following Reduced Intensity Conditioning in Treating Patients With Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: anti-thymocyte globulin
* Drug: busulfan
* Drug: fludarabine phosphate
* Procedure: allogeneic bone marrow transplantation
* Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of multiple myeloma, meeting 1 of the following criteria: Stage I disease with a bone lesion Stage II or III disease meeting any of the following criteria: Elevated beta-2 microglobulin Deletion of chromosome 13 Refractory or relapsed disease Presence of an evaluable monoclonal component Must have achieved reduction of primary tumor after receiving prior intensified chemotherapy with high-dose melphalan and cyclosporine with autologous transplantation HLA identical family donor available Bone marrow transplantation is allowed in case hematopoietic stem cell collection fails PATIENT CHARACTERISTICS: Karnofsky 70-100% No contraindications to allogeneic transplantation No contraindications to drugs used in conditioning regimen No psychiatric illness No other cancer within the past 5 years except basal cell skin cancer or epithelioma in situ of the cervix No serious and uncontrolled infection Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 1 month since participation in another prior clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: anti-thymocyte globulin|nan|
|Drug: busulfan|nan|
|Drug: fludarabine phosphate|nan|
|Procedure: allogeneic bone marrow transplantation|nan|
|Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate at 1 year |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, osteolytic lesions of multiple myeloma