p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Refractory/Relapsed Lymphoid Malignancies

Brief Title

p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Refractory/Relapsed Lymphoid Malignancies

Official Title

p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Refractory/Relapsed Lymphoid Malignancies

Brief Summary

      The purpose of this study is to evaluate how well the study drug works and safety of oral
      decitabine in patients with refractory or relapsed lymphoid malignancies. The decitabine is
      being given at a lower dose than used for its approved use. It is also being given with
      another drug, tetrahydrouridine (THU), to improve the exposure of lymphoma cells to
      decitabine.
    

Detailed Description

      Primary objective: To determine the objective response rate to oral THU-Dec in patients with
      3 separate biologic subsets of refractory/relapsed lymphoid malignancies:

        1. T-cell lymphoma,

        2. Aggressive B cell lymphoma,

        3. indolent B-cell lymphoma .

      Secondary objectives:

      (i) To evaluate the toxicity of oral THU-Dec in these patients; (ii) To evaluate hypotheses
      regarding mechanisms of resistance and predictive biomarkers.
    

Study Phase

Early Phase 1

Study Type

Interventional

Primary Outcome

Objective Response by Revised Response Criteria for Malignant Lymphoma

Secondary Outcome

 Complete Response

Condition

T-cell Lymphoma

Intervention

Decitabine

Study Arms / Comparison Groups

 Decitabine + Tetrahydrouridine

Description:  oral THU dosed by weight, followed by oral decitabine dosed by weight for 60 minutes (± 10 minutes) after the THU, twice weekly on consecutive days.
Treatment on protocol monitoring continues for 52 weeks.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

7

Start Date

April 25, 2017

Completion Date

January 22, 2018

Primary Completion Date

January 22, 2018

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically-proven T- or B-cell lymphoma

          -  Subjects must have received 1 or more prior therapies for this disease and have had
             stable disease or progressive disease based upon the criteria from the Revised
             Response Criteria for Malignant Lymphoma78, or intolerable toxicities precluding
             further therapy with a prior regimen

          -  Subjects must have measurable disease per Revised Response Criteria for Malignant
             Lymphoma78

          -  ECOG performance status 0 - 2

          -  Adequate organ function as defined by the following criteria:

               -  Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase
                  [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase
                  [SGPT]) ≤ 2.5 x laboratory upper limit of normal (ULN)

               -  Total serum bilirubin ≤ 2.0 x ULN (except if Gilbert's disease)

               -  Absolute neutrophil count (ANC) ≥ 1500/uL

               -  Platelets ≥ 50,000/uL

               -  Hemoglobin ≥ 8.0 g/dL (transfusion permitted)

               -  Serum calcium ≤ 12.0 mg/dL

               -  Serum Creatinine ≤ 3.0 mg/dL

          -  Patients with history of CNS lymphoma can be enrolled if the CNS disease has been
             controlled with therapy for a minimum of 4 weeks. Brain MRI is not required for
             eligibility.

          -  Subjects must have the ability to understand and the willingness to sign a written
             informed consent document.

        Exclusion Criteria:

          -  Life expectancy ≤ 4 months in the judgment of the treating clinician

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness (HIV-positive subjects on combination antiretroviral therapy
             are ineligible because of the potential for pharmacokinetic interactions with oral
             THU-Dec. Appropriate studies will be undertaken in subjects receiving combination
             antiretroviral therapy when indicated.

          -  Pregnancy or breastfeeding (pregnant or breastfeeding women are excluded from this
             study because oral THU-Dec has the potential for teratogenic or abortifacient effects.
             Because there is an unknown, but potential, risk for adverse events in nursing infants
             secondary to treatment of the mother with oral THU-Dec, breastfeeding should be
             discontinued if the mother is treated with oral THU-Dec.

          -  Other severe acute or chronic medical or psychiatric conditions or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the patient inappropriate for entry into
             this study.

          -  Receiving other investigational agent
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Brian Hill, MD, PhD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT02846935

Organization ID

CASE1416

Responsible Party

Sponsor-Investigator

Study Sponsor

Yogen Saunthararajah

Study Sponsor

Brian Hill, MD, PhD, Principal Investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Verification Date

January 2019