Clinical trial NCT00217438
Conditions: Refractory Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma
Sponsor: Fred Hutchinson Cancer Center
Start date: 2005-07-01; Completion date: 2012-10-01
Enrollment: 130 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Giving chemotherapy drugs, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy. Giving chemotherapy with a peripheral stem cell transplant once or twice, using stem cells from the patient or an identical brother or sister, may allow more chemotherapy to be given so more cancer cells are killed. Giving maintenance therapy after a stem cell transplant may kill any cancer cells that remain. It is not yet known which dose of melphalan is more effective in treating multiple myeloma (MM).

PURPOSE: This randomized phase III trial is studying two different doses of melphalan to compare how well they work when given together with amifostine followed by one or two autologous or syngeneic stem cell transplants and maintenance therapy in treating patients with stage II-III MM

Detailed description:
PRIMARY OBJECTIVES:

I. Compare the complete response (CR) and near CR rate in patients undergoing autologous stem cell transplant (ASCT) using melphalan 280 mg/m\^2 or melphalan 200 mg/m\^2.

SECONDARY OBJECTIVES:

I. Compare toxicities between patients receiving amifostine and melphalan 280 mg/m\^2 or melphalan 200 mg/m\^2.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

INDUCTION THERAPY:

ARM I (HIGH DOSE MELPHALAN AND AMIFOSTINE): Patients receive amifostine intravenously (IV) over 3-5 minutes on days -3 and -2 followed by high-dose melphalan IV over 15-30 minutes on day 2.

ARM II (LOW DOSE MELPHALAN AND AMIFOSTINE): Patients receive amifostine as in arm I and melphalan as in arm I at a lower dose.

AUTOLOGOUS OR SYNGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT): At least 20 hours after completion of melphalan, patients undergo autologous or syngeneic PBSCT on day 0.

Patients undergo restaging of the disease between days 80-90. Patients with progressive disease are removed from the study. Patients who achieve a CR or near-CR can proceed to optional maintenance therapy. Patients who do not achieve a CR or near-CR may undergo additional induction therapy as in arm I followed by a second autologous or syngeneic PBSCT.

Patients again undergo restaging of the disease 80-90 days later. Patients with progressive disease are removed from the study. Patients without progressive disease can proceed to maintenance therapy.

After completion of study treatment, patients are followed up every 3 months for 5 years.

Arms: arm 1: INDUCTION THERAPY:

Patients receive amifostine IV over 3-5 minutes on days -3 and -2 followed by high-dose melphalan IV over 15-30 minutes on day 2.

AUTOLOGOUS OR SYNGENEIC PBSCT: At least 20 hours after completion of melphalan, patients undergo autologous or syngeneic PBSCT on day 0.

Patients undergo restaging of the disease between days 80-90. Patients with progressive disease are removed from the study. Patients who achieve a CR or near-CR can proceed to optional maintenance therapy. Patients who do not achieve a CR or near-CR may undergo additional induction therapy as in arm I followed by a second autologous or syngeneic PBSCT.

Patients again undergo restaging of the disease 80-90 days later. Patients with progressive disease are removed from the study. Patients without progressive disease can proceed to maintenance therapy. arm 2: INDUCTION THERAPY:

Patients receive amifostine as in arm I and melphalan as in arm I at a lower dose.

AUTOLOGOUS OR SYNGENEIC PBSCT: At least 20 hours after completion of melphalan, patients undergo autologous or syngeneic PBSCT on day 0.

Patients undergo restaging of the disease between days 80-90. Patients with progressive disease are removed from the study. Patients who achieve a CR or near-CR can proceed to optional maintenance therapy. Patients who do not achieve a CR or near-CR may undergo additional induction therapy as in arm I followed by a second autologous or syngeneic PBSCT.

Patients again undergo restaging of the disease 80-90 days later. Patients with progressive disease are removed from the study. Patients without progressive disease can proceed to maintenance therapy.
Interventions: intervention 1: melphalan intervention 2: amifostine trihydrate intervention 3: peripheral blood stem cell transplantation intervention 4: fluorescence in situ hybridization intervention 5: bone marrow ablation with stem cell support
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Undergo PBSCT intervention 4: Correlative study intervention 5: Undergo transplant

Protocol documents: