A Study of Intensive-Dose Melphalan, Topotecan, and VP-16 Phosphate (MTV) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma
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
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of mucositis
to determine the incidence and duration of CTCAE v3, grade 3 or 4 mucositis for modified dose level four.
Daniel M. Sullivan, MD
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|