MGCD0103 Administered in Combination With Azacitidine (Vidaza®) to Subjects With Relapsed or Refractory Hodgkin or Non-Hodgkin Lymphoma
The first part of the study is to evaluate and determine if three different forms of MGCD0103 (free base FB-MGCD0103, tartaric acid free base [TA-FB-MGCD0103], and dihydrobromide [2HBr] salt formulation MGCD0103) have the same properties when given to patients with cancer. The second part of the study is to determine whether MGCD0103 administered in combination with azacitidine is effective and safe in treating subjects with relapsed or refractory Hodgkin's lymphoma or non-Hodgkin's lymphoma (NHL) (follicular or diffuse large B-cell [DLBCL]).
Non-Hodgkin Lymphoma (Follicular or Large Diffuse B-cell Lymphoma or Mantle Cell Lymphoma)
Drug: MGCD0103 and Azacitidine
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2, Open-label Trial to Evaluate the Efficacy and Safety of MGCD0103 Administered in Combination With Azacitidine (Vidaza®) to Subjects With Relapsed or Refractory Hodgkin or Non-Hodgkin Lymphoma, and to Evaluate the Pharmacokinetics of Different Formulations of MGCD0103|
- Primary efficacy is measured by: 1) PET, CT & physical exam, 2) overall response rate (complete response=disease is gone, partial response=disease has improved). Study treatment continues as long as the cancer is stable & side effects are tolerable. [ Time Frame: every other cycle of 28 days each ] [ Designated as safety issue: No ]
- Duration of response defined as: 1)the time of first documented objective response (either complete response or partial response) until the subject's disease gets worse, 2)how long his/her disease is stable. [ Time Frame: 28 days after the last study drug ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2007|
|Study Completion Date:||March 2009|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
Drug: MGCD0103 and Azacitidine
In Part 1 of the study, up to 22 people to enroll will receive a single, oral dose (75 mg gelcap) of MGCD0103 and FB-MGCD0103 during their first 2 weeks in the study. Up to 22 additional people will receive a single dose of both MGCD0103 and TA-FB-MGCE0103. The next group of people to enroll will receive 2 different single doses (25, 50, 100 mg) of FB-MGCD0103 or TA-FB-MGCD0103 during their first 2 weeks in the study.
In Part 2 of the study, from Day 1-5 of each 28-day cycle, all subjects will receive a dose of azacitidine (75 mg/m2) either subcutaneously or through an intravenous device, and on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, a single, oral dose (85 mg) of MGCD0103 until progression or unacceptable toxicity develops.
Other Name: Vidaza®
MGCD0103 and FB-MGCD0103 belong to a class of drugs known as histone deacetylase inhibitors (also called HDAC inhibitors). Azacitidine belongs to a class of anti-cancer drugs known as DNA de-methylating agents. Azacitidine (Vidaza®) was approved by the Food and Drug Administration (FDA) in 2004 for the treatment of myelodysplastic syndromes (MDS).
The combination of MGCD0103 and azacitidine has been given to about 50 people with leukemia or MDS in other clinical studies. This is the first study where the combination will be tested in people with lymphoma. Specifically, the study is designed to understand the following:
- How long single doses of TA-FB-MGCD0103, FB-MGCD0103 and MGCD0103 stay in the body, OR
- How long different doses of TA-FB-MGCD0103 and FB-MGCD0103 stay in the body; and
- How long MGCD0103 stays in the body when given with azacitidine; and
- What effect MGCD0103 and azacitidine have on the body and the study subject's type of lymphoma; and
- If the genetic and chemical make-up of the study subject's blood and/or tumor play a role in how she/he responds or does not respond to MGCD0103 and azacitidine.
|United States, Indiana|
|St. Francis Cancer Research Foundation|
|Beech Grove, Indiana, United States, 46107|
|United States, Nevada|
|Nevada Cancer Institute|
|Las Vegas, Nevada, United States, 89135|
|United States, New York|
|Weill Medical College of Cornell University|
|New York, New York, United States|
|United States, Texas|
|University of Texas, MD Anderson|
|Houston, Texas, United States, 77030|
|Study Director:||Gregory Reid, MSc, MBA||MethylGene Inc.|