Safety of Vorinostat in Combination With Bortezomib, Doxorubicin and Dexamethasone (VBDD) in Patients With Refractory or Relapsed Multiple Myeloma, A Phase I/II Study, Short Title: VBDD
A first cohort of three patients will be treated at the starting dose level of Vorinostat
100 mg/d, on day 1-4, 8-11, and 15-18 in combination with BDD.
The dose level of Vorinostat will be escalated in each new cohort:
if no dose limiting toxicity (DLT) has been observed in the previous dose level in 3
patient, the second cohort of 3 new patients will be treated with Vorinostat 200 mg/d and
the third cohort will be given Vorinostat with 300 mg/d.
Bortezomib will be administered intravenously (i.v.) 1.3mg/m2 d1, 8, 15. Doxorubicin will be
administered i.v. with a total dose of 18 mg/m2 per cycle (9 mg/m2, d1 and 8).
Dexamethasone will be administered per os (p.o.) with 40mg (first cycle) and 20mg (all other
subsequent cycles) on d1, 8, 15, 22.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximal Tolerated Dose (MTD)
The Maximal Tolerated Dose (MTD) is estimated as the highest dose at which less than two DLTs in 6 patients are observed in the first cycle. MTD estimation is based on the phase I part of the trial. However, the number of DLT's in the first cycle of the phase II patients will be inspected and discussed as well. The primary target variable is the occurrence of any dose-limiting toxicity (DLT) in MM patients during the first 28 days of treatment.
28 days (within first treatment cycle)
Monika Engelhardt, MD
University of Freiburg Medical School
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte, Klinische Studien, Kurt-Georg-Kiesinger-Allee 3,53175 Bonn