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

Institut Paoli-Calmettes

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma and Plasma Cell Neoplasm

Treatments: Drug: fludarabine phosphate; Drug: busulfan; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Biological: anti-thymocyte globulin; Procedure: allogeneic bone marrow transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT00802568

CDR0000626720

INCA-RECF0428

EUDRACT-2005-01053-13

IPC-ITT 04-02

IPC-2005-002

JANSSEN-IPC-2005-002

AMGEN-IPC-2005-002

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 48 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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