Clinical trial NCT03110354: DS-3201b for Acute Myelogenous Leukemia (AML) or Acute Lymphocytic Leukemia (ALL)
Official title: A Phase 1 Study of DS-3201b in Subjects With Acute Myelogenous Leukemia (AML) or Acute Lymphocytic Leukemia (ALL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Leukemia, Lymphocytic, Acute
Keywords: AML
ALL
Enhancer of zeste homolog (EZH) inhibitor
DS-3201b
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2017-04-12
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Has AML or ALL and failed any prior induction therapy regimen or have relapsed after prior therapy
2. Has Eastern Cooperative Oncology Group (ECOG) performance status 0-2
3. Has adequate renal and hepatic function
4. 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)
5. 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.
6. Agrees to use an adequate method of contraception during the study and until 3 months after the last treatment.
7. Is willing to provide bone marrow biopsies and comply with protocol-defined evaluations
8. Has a life expectancy of at least 3 months

Exclusion Criteria:

1. Has presence of central nervous system (CNS) involvement of leukemia or a history of CNS leukemia
2. Has a second concurrent active primary malignancy such as solid tumor or lymphoma under active treatment
3. 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)
4. 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
5. Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor
6. Has unresolved toxicities from previous anticancer therapy
7. Has received hematopoietic stem cell transplantation (HSCT) within 60 days of the first dose of DS-3201b
8. 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
9. 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
10. Had major surgery within 4 weeks before study drug treatment
11. 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)
12. Is pregnant or breastfeeding
13. 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
14. Has received prior treatment with enhancer of zeste homolog (EZH) inhibitor

Primary outcomes:
measure: Number of Participants With Any Grade Treatment-emergent Adverse Event Classified as Dose-limiting Toxicities (Dose Escalation)
timeFrame: Baseline up to Day 28
measure: Number of Participants Who Experienced Any Grade Treatment-emergent Adverse Event (Dose Escalation)
timeFrame: Baseline up to 30 days after last study dose, up to approximately 4 years
Secondary outcomes:
measure: Pharmacokinetic Parameter Maximum (Peak) Observed Concentration (Cmax) of DS-3201b
timeFrame: Cycle 1 Days 1 and 8 predose, 0.5, 1, 2, 4, 6, and 8 hours and Cycle 1 Day 15 postdose (each cycle is 28 days)
measure: Pharmacokinetic Parameter Time to Maximum Observed Concentration (Tmax) of DS-3201b
timeFrame: Cycle 1 Days 1 and 8 predose, 0.5, 1, 2, 4, 6, and 8 hours and Cycle 1 Day 15 postdose (each cycle is 28 days)
measure: Pharmacokinetic Parameter Area Under Plasma Concentration-Time Curve of DS-3201b
timeFrame: Cycle 1 Days 1 and 8 predose, 0.5, 1, 2, 4, 6, and 8 hours and Cycle 1 Day 15 postdose (each cycle is 28 days)
measure: Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) of DS-3201b
timeFrame: Cycle 1 Day 2 postdose (each cycle is 28 days)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: