Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma
Condition: Multiple Myeloma; Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation
      may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

      PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus
      peripheral stem cell transplantation in treating patients who have multiple myeloma.
    

Detailed description: 
      OBJECTIVES: I. Determine the toxicity and potential efficacy of intensive high dose
      chemotherapy consisting of melphalan, topotecan, and etoposide phosphate followed by
      autologous stem cell transplantation in patients with stage II or III multiple myeloma or
      stage I with evidence of progressive disease. II. Determine the maximum tolerated dose of
      topotecan in combination with melphalan and etoposide phosphate in this patient population.
      III. Determine response rates and time to treatment failure in these patients when treated
      with this regimen. IV. Determine the pharmacokinetic profiles of these drugs and investigate
      the pharmacodynamic relationships with respect to the efficacy and toxicity of this regimen
      in these patients. V. Determine whether the sequencing of this chemotherapy regimen is
      appropriate and optimal in these patients.

      OUTLINE: This is a dose escalation study of topotecan. Patients are primed with
      cyclophosphamide IV over 2 hours for 2 days. Peripheral blood stem cells (PBSC) are
      collected. Approximately 4 weeks after PBSC collection, patients receive melphalan IV over 30
      minutes and topotecan IV over 30 minutes on days -7 to -5. Etoposide phosphate IV is
      administered over 4 hours on days -4 and -3. PBSC are reinfused on day 0. Cohorts of 4-12
      patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is
      determined. The MTD is defined as the dose preceding that at which 6 of 12 patients
      experience dose limiting toxicities. Patients are followed 2-3 times a week for approximately
      1 month, then at 3, 6, and 12 months.

      PROJECTED ACCRUAL: A total of 34-60 patients will be accrued for this study within 24-36
      months.
    

Intervention name(s): etoposide phosphate; melphalan; topotecan; Autologous Stem Cell Rescue
Intervention type(s): Drug; Drug; Drug; Procedure
Intervention description(s): Etoposide phosphate 1363 mg/m^2/day IV over 4 hours (total dose 2726 mg/m^2, or 2400 mg/m^2 etoposide equivalents), beginning 24 hours after the completion of the last infusion of topotecan Days -4, -3; Melphalan 50 mg/m^2/day IV over 30 minutes (total dose 150 mg/m^2), followed immediately by topotecan. Days -7, -6, -5; Topotecan 3.3 mg/m^2/day (starting total dose = 10 mg/m^2 for level 2) IV over 30 minutes. No topotecan will be administered on the first dose level Days -7, -6, -5; reinfusion of stem cells, Day 0
Other intervention name(s): Topotecan; Alkeran(R); Autologous stem cell transplant
Intervention MeSH terms: Etoposide; Melphalan; Topotecan; Etoposide phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: refractory multiple myeloma; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma