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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


Phase 2
18 Years
N/A
Not Enrolling
Both
Hodgkin Lymphoma, Non-Hodgkin Lymphoma (Follicular or Large Diffuse B-cell Lymphoma or Mantle Cell Lymphoma)

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Trial Information

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


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.


Inclusion Criteria:



- Age ≥ 18 years.

- Histologically confirmed diagnosis of classical Hodgkin's lymphoma or NHL
(follicular, DLBCL, or mantle cell) and confirmed relapsed or refractory disease.
1)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. 2)Subjects
with DLBCL must be ineligible for, or have refused, autologous stem cell transplant,
or have relapsed following transplant. 3)Subjects with MCL must have relapsed after
prior treatment and not be eligible for autologous stem cell transplant (ASCT) or
have relapsed following ASCT. 4)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.

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 Evidence of
measurable disease (ie, at least one lesion that can accurately be measured in at
least two dimensions as ≥15 mm with spiral CT scan). 1)If only single target lesion
must be PET positive, and measure ≥20mm in two dimensions (required only for subjects
with Hodgkin's lymphoma and DLBCL).

- Adequate organ function including: 1)Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
(≥1500/mm^3); and 2)Platelets ≥ 50 x 10^9/L (≥50,000/mm^3); and 3)Total bilirubin ≤
1.5 x upper limit of normal (ULN) (unless increased due to Gilbert's Syndrome or
hemolysis); and 4)AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN; and 5)Serum creatinine ≤ 1.5
x ULN.

- 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.

- 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.

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

Exclusion Criteria:

- Prior HDAC inhibitor and azacitidine combination therapy.

- Known hypersensitivity to azacitidine, HDAC inhibitors, and/or any components of
MGCD0103, FB-MGCD0103, or TA-FB-MGCD0103 capsules and or azacitidine formulation
components.

- 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®).

- Previous or concurrent malignancy except adequately treated basal cell or squamous
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.

- Presence of significant involvement of the liver by lymphoma and impaired synthetic
function as indicated by hypoalbuminemia of < 1.0 x LLN.

- Active and uncontrolled clinically significant infection.

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

- Known infection with human immunodeficiency virus (HIV).

- History of melena or hematemesis within the last 3 months.

- Known central nervous system metastases.

- Less than 4 weeks elapsed since any major surgery.

- 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.

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

- Concurrent chronic treatment with therapeutic doses of systemic steroids.

- Prior or active disease or conditions 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

every other cycle of 28 days each

Safety Issue:

No

Principal Investigator

Gregory Reid, MSc, MBA

Investigator Role:

Study Director

Investigator Affiliation:

MethylGene Inc.

Authority:

United States: Food and Drug Administration

Study ID:

103 PH US 2007 CL002

NCT ID:

NCT00543582

Start Date:

October 2007

Completion Date:

March 2009

Related Keywords:

  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma (Follicular or Large Diffuse B-cell Lymphoma or Mantle Cell Lymphoma)
  • Hodgkin Disease
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Mantle-Cell

Name

Location

Weill Medical College of Cornell UniversityNew York, New York  10021
Nevada Cancer InstituteLas Vegas, Nevada  89135
St. Francis Cancer Research FoundationBeech Grove, Indiana  46107
University of Texas, MD AndersonHouston, Texas  77030