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

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

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.

Study Overview

• Status: Terminated
• Conditions: Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Acute
• Intervention / Treatment: Drug: DS-3201b

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DS-3201b 100 mg; Participants who received 100 mg DS-3201b administered orally to participants with AML or ALL.	Drug: DS-3201b; DS-3201b is supplied as 25 and 100 mg capsules packaged in high-density polyethylene (HDPE) bottles.
Experimental: DS-3201b 150 mg; Participants who received 150 mg DS-3201b administered orally to participants with AML or ALL.	Drug: DS-3201b; DS-3201b is supplied as 25 and 100 mg capsules packaged in high-density polyethylene (HDPE) bottles.
Experimental: DS-3201b 250 mg; Participants who received 250 mg DS-3201b administered orally to participants with AML or ALL.	Drug: DS-3201b; DS-3201b is supplied as 25 and 100 mg capsules packaged in high-density polyethylene (HDPE) bottles.
Experimental: DS-3201b 500 mg; Participants who received 500 mg DS-3201b administered orally to participants with AML or ALL.	Drug: DS-3201b; DS-3201b is supplied as 25 and 100 mg capsules packaged in high-density polyethylene (HDPE) bottles.
Experimental: DS-3201b 700 mg; Participants who received 700 mg DS-3201b administered orally to participants with AML or ALL.	Drug: DS-3201b; DS-3201b is supplied as 25 and 100 mg capsules packaged in high-density polyethylene (HDPE) bottles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Grade Treatment-emergent Adverse Event Classified as Dose-limiting Toxicities (Dose Escalation)	Dose-limiting toxicity (DLT) is defined as a clinically significant non-hematologic treatment-emergent adverse event (TEAE) or abnormal clinical laboratory value that is clearly not related to disease progression, intercurrent illness, and occurring during the first cycle (28 days) on study that meets any of the following criteria: National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Grade 3 aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), or bilirubin for ≥7 days; NCI-CTCAE Grade 4 AST (SGOT) or ALT (SGPT) of any duration; All Grade 4 non-hematologic toxicities of any duration; Any Grade 5 toxicity, unless proven to be clearly and incontrovertibly related to disease progression or intercurrent illness will constitute a DLT; All other clinically significant, non-hematological NCI-CTCAE Grade 3/4 AEs. AEs were coded using the MedDRA dictionary, Version 23.0.	Baseline up to Day 28
Number of Participants Who Experienced Any Grade Treatment-emergent Adverse Event (Dose Escalation)	A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug or has worsened after initiating the study drug until 30 days after the last dose of the study drug. AEs were coded using the MedDRA dictionary, Version 23.0.	Baseline up to 30 days after last study dose, up to approximately 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameter Maximum (Peak) Observed Concentration (Cmax) of DS-3201b	Pharmacokinetic parameters were assessed using noncompartmental methods.	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)
Pharmacokinetic Parameter Time to Maximum Observed Concentration (Tmax) of DS-3201b	Blood samples were collected for PK analysis. PK parameters were assessed using noncompartmental methods.	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)
Pharmacokinetic Parameter Area Under Plasma Concentration-Time Curve of DS-3201b	Blood samples were collected for PK analysis. Area under the plasma concentration-time curve up to 24 hours (AUC24h) and area under the plasma concentration-time curve up to the last measurable concentration (AUClast) were assessed using noncompartmental methods.	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)
Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) of DS-3201b	Blood samples were collected for PK analysis. PK parameters were assessed using noncompartmental methods.	Cycle 1 Day 2 postdose (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2017
• Primary Completion (Actual): March 9, 2021
• Study Completion (Actual): March 9, 2021

Study Registration Dates

• First Submitted: March 31, 2017
• First Submitted That Met QC Criteria: April 6, 2017
• First Posted (Actual): April 12, 2017

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: AML; ALL; DS-3201b; Enhancer of zeste homolog (EZH) inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: DS3201-A-U102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No