MDACC Study Summary 2007-0536 (Archived)

Study Summary
No. 2007-0536:.......Lymphoma......Anas Younes......Lymphoma/Myeloma

Study Summary Title



Study Summary Number:	2007-0536

Study 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

Physician

New Patient Referral



Name:	Anas Younes	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Lymphoma/Myeloma	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2860 Contact us about clinical trials

General Information



Disease Group:	Lymphoma	Supported By:	Methylgene Pharmion

Phase of Study:	Phase II	Return Visit:	Part 1 - After the first & second doses - Days 1-3. Part 2 - Days 1-5; Days 8, 15, 22 and 28.

Treatment Agents:	Azacytidine FB-MGCD0103 MGCD0103 TA-FB-MGCD0103	Home Care:	N/A

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	N/A

Description/
Intervention:

This study will be done in 2 parts. The goal of Part 1 of this clinical
research study is learn how long MGCD0103, FB-MGCD0103, and TA-FB-MGCD0103 stay
in the body. This is called pharmacokinetic (PK) testing. Researchers would
also like to find out if these 3 different forms of MGCD0103 act the same when
given to patients with cancer.

The goals of Part 2 of this clinical research study is to learn if MGCD0103 and
Vidaza® (azacitidine) can help to control the disease in patients with Hodgkin
or non-Hodgkin lymphoma that cannot be cured by surgery, drugs, or any other
known treatments. Researchers will also study if the genetic and chemical
make-up of your blood and/or tumor affect how you respond when these two drugs
are given together. This is called pharmacodynamic (PD) testing.

Study Objectives / Outcomes

The primary objectives of the study are to:

determine the overall objective response rate (ORR = Partial Responses [PRs] + Complete Responses [CRs]) of MGCD0103 (dihydrobromide [2HBr] salt formulation) administered in combination with azacitidine to subjects with relapsed or refractory Hodgkin lymphoma or non-Hodgkin lymphoma (NHL) (follicular lymphoma,diffuse large B-cell lymphoma [DLBCL], or mantle cell lymphoma [MCL]);
to evaluate the pharmacokinetics (PK) of MGCD0103 (dihydrobromide salt formulation), FB-MGCD0103 (free base formulation), and TA-FB-MGCD0103 (tartaric acid free base formulation), and to establish bioequivalence (BE) between FB-MGCD0103 and MGCD0103 or between TA-FB-MGCD0103 and MGCD0103; and
to determine the dose proportionality of FB-MGCD0103 or TA-FB-MGCD0103

Secondary objectives are to:

assess the duration of progression-free survival (PFS); and
estimate the time to, and duration of, objective responses (PRs + CRs); and
assess the safety profile of MGCD0103 administered in combination with azacitidine to subjects with relapsed or refractory Hodgkin lymphoma or NHL (follicular lymphoma, DLBCL, or MCL); and
evaluate potential pharmacodynamic markers and biomarkers in the study population.

Study Status Information



Study Activation / Registration Date:

IRB Review and Approval Date:	12/12/2007

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Terminated

Projected Accrual:	96

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Age >/= 18 years

2) Histologically confirmed diagnosis of classical Hodgkin's lymphoma, or NHL (follicular lymphoma, DLBCL or MCL) and confirmed relapsed or refractory disease: a.) Subjects with a diagnosis of classical Hodgkin's lymphoma must have relapsed following a prior autologous, allogeneic or reduced intensity allogeneic stem cell transplant. Subjects who received an allogeneic transplant must have no evidence of graft versus host disease (GVHD), and have discontinued treatment with immunosuppressive agents >/= 3 months prior to enrollment in this study. (cont in # 3)

3) (cont. from # 2) (b.) Subjects with DLBCL must be ineligible for, or have refused, autologous stem cell transplant, or have relapsed following transplant. (c.) Subjects with MCL must have relapsed after prior treatment and not be eligible for autologous stem cell transplant (ASCT), or have relapsed following ASCT. (d.) Subjects with NHL who may have received a prior allogeneic stem cell transplant must have no evidence of GVHD, and have discontinued treatment with immunosuppressive agents >/= 3 months prior to enrollment in this study;

4) Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

5) Evidence of measurable disease (i.e., multiple target lesions that can accurately be measured in two dimensions as >/= 15 mm with spiral CT scan): If only single target lesion measuring >/= 20 mm in two dimensions, lesion must be PET positive (required only for subjects with Hodgkin's lymphoma and DLBCL);

6) Adequate organ function, including: a.) Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L (>/= 1500/mm^3); and b.) Platelets >/= 50 x 10^9/L (>/= 50,000/mm^3); and c.) Total bilirubin </= 1.5 x upper limit of normal (ULN) (unless increased due to Gilbert's Syndrome or hemolysis); and d.) AST (SGOT) and ALT (SGPT) </= 2.5 x ULN; and e.) Serum creatinine </= 1.5 x ULN;

7) At least 3 weeks elapsed since any prior anticancer therapy (standard or investigational) and full recovery (NCI CTCAE grade 1) from the toxic effects of that treatment;

8) For women of childbearing potential a negative serum pregnancy test within 7 days of treatment, a negative urine pregnancy test immediately prior to the first treatment with study drugs, and use of 2 physician-approved methods of birth control throughout the study and for a period of 3 months following the study; and

9) Written informed consent, willingness, and ability to comply with all study procedures.

Exclusion Criteria:

1) Prior HDAC inhibitor and azacitidine combination therapy;

2) Known hypersensitivity to azacitidine, HDAC inhibitors, and/or any components of MGCD0103, TA-FB-MGCD0103 and/or FB-MGCD0103 capsules or azacitidine formulation components (i.e., mannitol);

3) Any condition that will put the subject at undue risk or discomfort as a result of adherence to study procedures (eg, requirement to take MGCD0103 with Gatorade®);

4) Previous or concurrent malignancy except adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry;

5) Presence of significant involvement of the liver by lymphoma and impaired synthetic function as indicated by hypoalbuminemia of < 1.0 x LLN;

6) Active and uncontrolled clinically significant infection;

7) Known Hepatitis B surface antigen (HepB SAg) positive or Hepatitis C antibody positive

8) Known infection with human immunodeficiency virus (HIV);

9) History of melena, hematemesis, or hemoptysis within the last 3 months;

10) Known central nervous system metastases;

11) Less than 4 weeks elapsed since any major surgery;

12) Pregnant or lactating women. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of beginning Part 1 of the study.

13) WOCBP and men whose partners are WOCBP must use two acceptable methods of contraception while enrolled on this study, and for a period of 3 months following study drug treatment. Subjects unwilling or unable to follow this guideline will be excluded.

14) Concurrent chronic treatment with therapeutic doses of systemic steroids

15) Prior or active disease or condition that, in the opinion of the investigator, may interfere with the procedures or evaluations to be conducted in the study. This includes, but is not limited to, uncontrolled intercurrent illnesses such as symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements

Links

Registration Number: NCT00543582
Study Information on Clinical Trials Registry (clinicaltrials.gov)