Phase I/II Study of 5-azacitidine in Combination With Vorinostat in Patients With Relapsed or Refractory DLBCL
Eligible subjects will have biopsy proven relapsed or refractory DLBCL, have preserved
hematologic and other organ function, and have either progressed following or be
inappropriate candidates for autologous stem cell transplantation.
Patients will be treated with 5-azacitidine via subcutaneous administration and vorinostat
orally at four different dose levels as described below:
- Dose level 1: azacitidine 55 mg/m2 on days 1-5 and oral vorinostat at 300 mg BID on
- Dose level 2: azacitidine 75 mg/m2 on days 1-5 and oral vorinostat at 200 mg BID on
- Dose level 3: azacitidine 55 mg/m2 on days 1-5 and oral vorinostat at 300 mg BID on
- Dose level 4: azacitidine 75 mg/m2 on days 1-5 and oral vorinostat at 200 mg BID on
Each cycle will be of 28 days and patients will be treated for up to 6 cycles.
Up to 8 patients will be enrolled at each dose level. If at any time 2 patients in a given
cohort experience DLT, enrollment to that level will be discontinued.
Efficacy will be assessed by standard radiographic and other criteria at baseline and at the
end of treatment to determine ORR. Patients will be followed for 2 years or until disease
Tumor samples will be obtained for correlative studies at baseline through core needle or
surgical biopsy, with an additional biopsy performed on day 15 of cycle 1 as a
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
determination of maximum tolerated dose (MTD) of azacitidine and vorinostat when given in combination as treatment for relapsed/refractory DLBCL
determine the safety and tolerability of the combination of azacitidine with vorinostat as measured by the occurrence of dose limiting toxicities during the first 28 days of treatment for each patient, and to determine an appropriate dose for further study
Rebecca Elstrom, MD
Weill Medical College of Cornell University
United States: Institutional Review Board
|Weill Cornell Medical College||New York, New York 10021|