Clinical trial NCT02846935: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: T-cell Lymphoma
Aggressive B-cell Lymphoma
Non-Hodgkin's Lymphomas
Indolent B-cell Lymphoma
Keywords: p16/CDKN2A
TP53
THU
Decitabine
Tetrahydrouridine
DEC
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2016-07-27
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response by Revised Response Criteria for Malignant Lymphoma
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Complete Response
timeFrame: Up to 52 weeks
measure: Partial Response
timeFrame: Up to 52 weeks
measure: Stable Disease
timeFrame: Up to 52 weeks
measure: Progressive Disease
timeFrame: Up to 52 weeks
measure: Duration of response
timeFrame: Up to 52 weeks
measure: Disease-free survival
timeFrame: Up to 52 weeks
measure: Disease-specific survival
timeFrame: Up to 52 weeks
measure: Progression-free survival
timeFrame: Up to 52 weeks
measure: Time to progression
timeFrame: Up to 52 weeks
measure: Time to treatment failure
timeFrame: Up to 52 weeks
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Brian Hill, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: