DS-3201b for Acute Myelogenous Leukemia (AML) or Acute Lymphocytic Leukemia (ALL)

Study Overview
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Brief Summary
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This research study tests an investigational drug called DS-3201b. An investigational drug is a medication that is still being studied and has not yet been approved by the United States Food and Drug Administration (FDA). The FDA allows DS-3201b to be used only in research. It is not known if DS-3201b will work or not. This study consists of two parts. The first part (Part 1) is a dose escalation that will enroll subjects with AML or ALL that did not respond or no longer respond to previous standard therapy. The purpose of Part 1 of this research study is to determine the highest dose a patient can tolerate or recommended dose of DS-3201b that can be given to subjects with AML or ALL. Once the highest tolerable dose is determined, additional subjects will be enrolled at that dose into Part 2 of the study.

Official Title
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A Phase 1 Study of DS-3201b in Subjects With Acute Myelogenous Leukemia (AML) or Acute Lymphocytic Leukemia (ALL)

Conditions
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Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Acute

Intervention / Treatment
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* Drug: DS-3201b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has AML or ALL and failed any prior induction therapy regimen or have relapsed after prior therapy Has Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Has adequate renal and hepatic function Had at least 14 days for prior treatment to clear the body before initiation of DS-3201b administration (except for hydroxyurea that needs only 2 days for clearance) Able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or comorbidity that would interfere with therapy. Agrees to use an adequate method of contraception during the study and until 3 months after the last treatment. Is willing to provide bone marrow biopsies and comply with protocol-defined evaluations Has a life expectancy of at least 3 months Exclusion Criteria: Has presence of central nervous system (CNS) involvement of leukemia or a history of CNS leukemia Has a second concurrent active primary malignancy such as solid tumor or lymphoma under active treatment Has refractory nausea and vomiting, malabsorption, biliary shunt, significant bowel resection, graft versus- host disease (GVHD) significantly affecting gut motility or absorption, or any other condition that would preclude adequate absorption of DS- 3201b in the opinion of the treating physician and/or principal investigator (PI) Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or tested positive for active hepatitis B or C infection Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor Has unresolved toxicities from previous anticancer therapy Has received hematopoietic stem cell transplantation (HSCT) within 60 days of the first dose of DS-3201b Has received concomitant treatment with a strong inhibitor or inducer of cytochrome P450 (CYP)3A4/5 within 7 days of first receipt of DS-3201b Has consumed herbs/fruits that may have an influence on pharmacokinetics (PK) of DS-3201b from 3 days (14 days for St. John's wort) prior to the start of the study and throughout the entire study Had major surgery within 4 weeks before study drug treatment Has prolonged corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is > 450 milliseconds (ms) based on triplicate electrocardiograms (ECGs) Is pregnant or breastfeeding Has substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the subject's participation in the clinical study or evaluation of the clinical study results Has received prior treatment with enhancer of zeste homolog (EZH) inhibitor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DS-3201b in AML or ALL<br>DS-3201b is administered orally to participants with AML or ALL at a starting dose of 100 mg once a day, and then possibly at higher doses depending on safety observations | Drug: DS-3201b<br>* DS-3201b is supplied as 25 and 100 mg capsules packaged in high-density polyethylene (HDPE) bottles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of participants with dose-limiting toxicities | Part 1 is the 28-day dose escalation part | within 28 days | 
| Part 2: Number of participants with dose-limiting toxicities | Part 2 is the dose expansion part | within 2 years | 
| Parts 1 and 2: Number of participants who experienced an adverse event during the trial | Adverse events are collected for the entire duration of study participation | within 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum (peak) observed concentration (Cmax) | Cmax is the highest concentration of the drug in circulating plasma (blood) as observed on days 1-2 and 8 of each part's single 28-day pharmacokinetics (PK) cycle. | within 8 days | 
| Time to maximum observed concentration (Tmax) | Tmax is the time it takes for Cmax to be reached as observed on days 1-2 and 8 of each part's single 28-day PK cycle. | within 8 days | 
| Area under the curve up to the last quantifiable time (AUClast) | Area under the plasma concentration-time curve up to the last measurable concentration as observed on days 1-2 and 8 of each part's single 28-day PK cycle. | within 8 days | 
| Trough plasma concentration (Ctrough) | Trough concentration is the lowest concentration reached by a drug before the next dose is administered as observed Pre-dose on Days 2, 8, 15, 22 in the single 28-day cycle 1, day 1 of cycle 2 and End of Treatment | within 2 years | 
| Part 2: Number of participants with response to treatment | Response to treatment is defined per the revised International Working Group (IWG) response criteria for AML (Cheson 2003) or standard response criteria for ALL (NCCN 2016 ALL response criteria) | within 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, ALL, Enhancer of zeste homolog (EZH) inhibitor, DS-3201b