Study of 5-azacitidine in Combination With Vorinostat in Patients With Relapsed or Refractory Diffuse Large b Cell Lymphoma (DLBCL)
Recruitment status was Recruiting
This will be a phase I/II study of 5-azacitidine in combination with vorinostat in patients with relapsed or refractory DLBCL. Combination therapy with methyltransferase inhibitors and histone deacetylase inhibitors is highly synergistic in DLBCL cells, and both classes of drugs can also synergize powerfully with standard anti-lymphoma chemotheraputics such as doxorubicin in pre-clinical studies. We hypothesize that azacytidine + vorinostat combination therapy will be safe and effective in selected patients with relapsed or refractory DLBCL. We also hypothesize that patients demonstrating objective responses to this combination therapy display specific epigenetic signatures, and that a biomarker or gene classifier can be generated which will identify those patients likely to respond.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of 5-azacitidine in Combination With Vorinostat in Patients With Relapsed or Refractory DLBCL|
- determination of maximum tolerated dose (MTD) of azacitidine and vorinostat when given in combination as treatment for relapsed/refractory DLBCL [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]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
- overall response rate [ Time Frame: at end of treatment (6 months) and for up to 2 years ] [ Designated as safety issue: No ]determine efficacy of the combination of 5-azacitidine with vorinostat in patients with relapsed and refractory DLBCL, as measured by overall response rate (ORR)
|Study Start Date:||September 2010|
|Estimated Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
|Experimental: all subjects||
Each cycle = 28 days. Subjects may receive up to 6 cycles.
Each cycle = 28 days. Subjects receive up to 6 cycles.
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 Days 1-7.
- Dose level 2: azacitidine 75 mg/m2 on days 1-5 and oral vorinostat at 200 mg BID on Days 1-7.
- Dose level 3: azacitidine 55 mg/m2 on days 1-5 and oral vorinostat at 300 mg BID on Days 1-14.
- Dose level 4: azacitidine 75 mg/m2 on days 1-5 and oral vorinostat at 200 mg BID on Days 1-14.
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 progression.
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 pharmacodynamic endpoint.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01120834
|Contact: Rebecca Elstrom Elstrom, MDfirstname.lastname@example.org|
|United States, New York|
|Weill Cornell Medical College||Recruiting|
|New York, New York, United States, 10065|
|Contact: Rebecca Elstrom, MD 646-962-2064 email@example.com|
|Principal Investigator: Rebecca Elstrom, MD|
|Principal Investigator:||Rebecca Elstrom, MD||Weill Medical College of Cornell University|