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

Leukemia, Myeloid, Acute Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03110354
• Other study ID #: DS3201-A-U102
• Status: Terminated
• Phase: Phase 1
• Start date: April 5, 2017
• Est. completion date: March 9, 2021

Study information

• Verified date: January 2024
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: March 9, 2021
• Est. primary completion date: March 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Acute
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• DS-3201b
DS-3201b is supplied as 25 and 100 mg capsules packaged in high-density polyethylene (HDPE) bottles.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Duke University	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	Vanderbilt University	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)