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

NCT ID: NCT02846935

Last Updated: 2019-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-25
• Study Completion Date: 2018-01-22

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.

Conditions

T-cell Lymphoma; Aggressive B-cell Lymphoma; Non-Hodgkin's Lymphomas; Indolent B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Decitabine + Tetrahydrouridine

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.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

2-4 capsules depending on the weight of participant. Dec capsules are ingested \~60 minutes after THU capsules.

Tetrahydrouridine

Intervention Type: DRUG

2-4 capsules depending on the weight of participant. Oral THU capsules followed 60 minutes later by oral Dec capsules are ingested 2X/week on consecutive days.

Interventions

Decitabine

2-4 capsules depending on the weight of participant. Dec capsules are ingested \~60 minutes after THU capsules.

Intervention Type: DRUG

Tetrahydrouridine

2-4 capsules depending on the weight of participant. Oral THU capsules followed 60 minutes later by oral Dec capsules are ingested 2X/week on consecutive days.

Intervention Type: DRUG

Other Intervention Names

DEC; THU

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yogen Saunthararajah

OTHER

Sponsor Role: lead

Responsible Party

Yogen Saunthararajah

Professor of Hematology and Oncology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Brian Hill, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Locations

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

CASE1416

Identifier Type: -

Identifier Source: org_study_id