Clinical Trial 19321

Cancer Type:
Interventions:5-azacitidine; FK228 (Romidepsin); Romidepsin; Vidaza (5-azacitidine); azacitidine (5-azacitidine)

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Lubomir Sokol

Overview

Study Title

Phase I/IIA Study of the Oral 5-Azacitidine in Combination with the Histone Deacetylase Inhibitor Romidepsin for the Treatment of Patients with T-Cell Lymphoma

Summary

The purpose of this research study is to confirm the tolerability and assess the preliminary efficacy (capacity for beneficial change or therapeutic effect) of romidepsin and oral azacitidine in patients with T-Cell Lymphoma.

Objective

A. Phase I Primary Objectives: Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combination of oral 5-azacitidine and romidepsin. Evaluate the safety and toxicity of the combination of oral 5-azacitidine and romidepsin. Secondary Objectives: Describe the maximum number of cycles received. Describe the number of dose delays and dose reductions at the MTD. Describe the anti-tumor activity of the combination. Evaluate the overall response rate (ORR), progression free survival (PFS), and duration of response (DOR) of the study population. Exploratory Objectives: Evaluate pharmacodynamic markers of drug effect in paired tissue biopsies (pre- and post- treatment) including gene expression and genome wide methylation patterns. Establish the pharmacokinetic profile for oral 5-azacitidine and romidepsin when given as a combination in Cycle 1 at various time intervals as listed in Figure 1. B. Phase II Primary Objectives: Estimate the ORR (complete + partial response) of the combination of oral 5-azacitidine and romidepsin in patients with relapsed/refractory T-cell Lymphoma. Secondary Objectives: Estimate the DOR and PFS of the combination in patients with T-cell lymphoma. Estimate the overall survival of patients with T-cell lymphoma on study. Identify potential pre-treatment biomarkers of response based on GEP and/or methylation array) to clinical outcome. Exploratory Objectives: Evaluate pharmacodynamic markers of drug effect in paired tissue biopsies (pre- and post- treatment) including gene expression and genome wide methylation patterns.

Inclusion Criteria

  • Phase I: Histologically confirmed relapsed or refractory non-Hodgkin lymphoma or Hodgkin lymphoma (WHO criteria), with no accepted curative options.
  • Phase II: Relapsed or refractory T-cell lymphoma, including patients with central nervous system (CNS) involvement or lymphomatous meningitis are allowed on study.
  • Relapsed or refractory disease following frontline chemotherapy. No upper limit for the number of prior therapies. > Patients may have relapsed after prior autologous or allogeneic stem cell transplant.
  • Evaluable Disease in the Phase I, and measurable disease for the Phase II.
  • Age > or = 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
  • Adequate organ and marrow function.
  • Negative urine or serum pregnancy test for females of childbearing potential.
  • Females of childbearing potential must use an effective barrier method of contraception during the treatment period and for at least 1 month thereafter. Male participants should use a barrier method of contraception during the treatment period and for at least 3 months thereafter.
  • Ability to understand and the willingness to sign a written informed consent document.

  • Exclusion Criteria

  • Prior Therapy: Exposure to chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier; Systemic steroids that have not been stabilized ( ≥ 5 days) to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs; No other concurrent investigational agents are allowed.
  • History of allergic reactions to Oral 5-azacitidine or Romidepsin.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Women who are pregnant or nursing.
  • Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, the patient must be disease-free for ≥ 3 years.
  • Known to be Human Immunodeficiency Virus (HIV)-positive.
  • Active hepatitis A, hepatitis B, or hepatitis C infection.
  • Concomitant use of CYP3A4 inhibitors.
  • Any known cardiac abnormalities.