Clinical Trials /

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

NCT03110354

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: DS3201-A-U102
  • NCT ID: NCT03110354

Conditions

  • Leukemia, Myeloid, Acute
  • Leukemia, Lymphocytic, Acute

Interventions

DrugSynonymsArms
DS-3201bDS-3201b in AML or ALL

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
DS-3201b in AML or ALLExperimentalDS-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
  • DS-3201b

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of participants with dose-limiting toxicities
Time Frame:within 28 days
Safety Issue:
Description:Part 1 is the 28-day dose escalation part

Secondary Outcome Measures

Measure:Maximum (peak) observed concentration (Cmax)
Time Frame:within 8 days
Safety Issue:
Description: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.
Measure:Time to maximum observed concentration (Tmax)
Time Frame:within 8 days
Safety Issue:
Description: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.
Measure:Area under the curve up to the last quantifiable time (AUClast)
Time Frame:within 8 days
Safety Issue:
Description: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.
Measure:Trough plasma concentration (Ctrough)
Time Frame:within 2 years
Safety Issue:
Description: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
Measure:Part 2: Number of participants with response to treatment
Time Frame:within 2 years
Safety Issue:
Description: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)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • AML
  • ALL
  • Enhancer of zeste homolog (EZH) inhibitor
  • DS-3201b

Last Updated

October 9, 2019