Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma; Plasma Cell Neoplasm

Treatments: Drug: tacrolimus; Biological: CD34+ cells; Drug: cyclophosphamide; Drug: methotrexate; Drug: melphalan; Drug: fludarabine phosphate; Biological: filgrastim

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00028600

CDR0000069109 (Registry Identifier)

U10CA031946 (U.S. NIH Grant/Contract)

CALGB-100001

Details and patient eligibility

About

RATIONALE: Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect).

PURPOSE: This phase II trial is studying how well autologous peripheral stem cell transplant followed by donor peripheral stem cell transplant works in treating patients with multiple myeloma.

Full description

OBJECTIVES:

• Determine whether autologous peripheral blood stem cell transplantation (PBSCT) followed by non-myeloablative allogeneic PBSCT is associated with no more than 20% treatment-related mortality rates at 6 months in patients with multiple myeloma.
• Determine the response rate of patients treated with this regimen.
• Determine the percent donor chimerism in patients treated with this regimen.
• Determine the rate of graft-vs-host disease in patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.
• Determine the disease-free and overall survival of patients treated with this regimen.
• Determine whether abnormal cytogenetics at presentation correlate with poor response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive cyclophosphamide IV over 1-2 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until peripheral blood stem cell (PBSC) collection is complete.

Approximately 2-4 weeks after PBSC collection, patients receive melphalan IV over 15-30 minutes on day -2. Patients then undergo autologous PBSC transplantation (PBSCT) on day 0. Patients receive G-CSF SC beginning on day 5 and continuing until blood counts recover.

Approximately 2-4 months after autologous PBSCT, patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV over 1 hour on days -4 to -3. Patients undergo allogeneic PBSCT on day 0. Patients receive G-CSF SC beginning on day 7 and continuing until blood counts recover.

Patients receive graft-vs-host disease (GVHD) prophylaxis comprising oral tacrolimus twice daily on days -1 to 90 followed by a taper on days 91-150 and methotrexate IV on days 1, 3, and 6.

After day 120, patients with stable or progressive disease and no evidence of active GVHD may receive donor lymphocyte infusion (DLI) over 2 hours. Patients may receive up to 3 DLIs every 8 weeks.

Patients are followed every 3 months for 3 years, every 6 months for 5 years, and then annually for 15 years.

PROJECTED ACCRUAL: A maximum of 63 patients will be accrued for this study.

Enrollment: 60 patients

Sex: All

Ages: Under 64 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of active multiple myeloma that requires treatment

  • Durie-Salmon stage I, II, and III

• No more than 1 progression after initial therapy

• Must have HLA-identical sibling donor (6/6) by serologic typing (A, B, DR)

  • No syngeneic donors

• Must also be enrolled on protocol CLB-8461 (Cytogenetic Studies in Acute Leukemia)

PATIENT CHARACTERISTICS:

Age:

• Under 65

Performance status:

• NCI CTC 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 500/mm^3
• Platelet count greater than 50,000/mm^3

Hepatic:

• Bilirubin less than 2 mg/dL
• AST less than 3 times upper limit of normal (ULN)
• Alkaline phosphatase less than 3 times ULN

Renal:

• Creatinine less than 2 mg/dL
• Creatinine clearance greater than 40 mL/min

Cardiovascular:

• LVEF at least 30% by MUGA scan

Pulmonary:

• DLCO greater than 40% of predicted
• No symptomatic pulmonary disease

Other:

• HIV negative
• No uncontrolled diabetes mellitus
• No active serious infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy
• Prior alkylating-agent therapy allowed if no more than 12 months duration

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• At least 4 weeks since prior surgery

Other:

• All prior therapy no more than 18 months duration

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Autologous + Allogeneic Transplant

Experimental group

Description:

autologous PB stem cell transplant followed by non-myeloablative allogeneic transplant fr multiple myeloma

Treatment:

Drug: tacrolimus

Drug: methotrexate

Drug: cyclophosphamide

Drug: melphalan

Drug: fludarabine phosphate

Biological: CD34+ cells

Biological: filgrastim