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

NCT02846935 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: CASE1416
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

p16/CDKN2A; TP53; THU; Decitabine; Tetrahydrouridine; DEC

Outcome Measures

Primary Outcomes (1)

• Objective Response by Revised Response Criteria for Malignant Lymphoma

  Up to 52 weeks

Secondary Outcomes (10)

• Complete Response

  Up to 52 weeks

• Partial Response

  Up to 52 weeks

• Stable Disease

  Up to 52 weeks

• Progressive Disease

  Up to 52 weeks

• Duration of response

  Up to 52 weeks

Study Arms (1)

Decitabine + Tetrahydrouridine

EXPERIMENTAL

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.

Drug: Decitabine; Drug: Tetrahydrouridine

Interventions

Decitabine DRUG

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

Also known as: DEC

Decitabine + Tetrahydrouridine

Tetrahydrouridine 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.

Also known as: THU

Decitabine + Tetrahydrouridine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Yogen Saunthararajah: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell

Interventions

Decitabine; Tetrahydrouridine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Uridine

Study Officials

• Brian Hill, MD, PhD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Hematology and Oncology

Study Record Dates

• First Submitted: July 25, 2016
• First Posted: July 27, 2016
• Study Start: April 25, 2017
• Primary Completion: January 22, 2018
• Study Completion: January 22, 2018
• Last Updated: January 7, 2019

Record last verified: 2019-01

Locations

US (1)