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

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03110354
• Collaborator: (none)
• Enrollment: 28
• Locations: 6
• Arm: 1
• Actual Duration (Months): 47.1
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Acute	Drug: DS-3201b	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Open label
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of DS-3201b in Subjects With Acute Myelogenous Leukemia (AML) or Acute Lymphocytic Leukemia (ALL)
• Actual Study Start Date: Apr 5, 2017
• Actual Primary Completion Date: Mar 9, 2021
• Actual Study Completion Date: Mar 9, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DS-3201b in AML or ALL 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; DS-3201b is supplied as 25 and 100 mg capsules packaged in high-density polyethylene (HDPE) bottles.

Outcome Measures

Primary Outcome Measures

1. Part 1: Number of participants with dose-limiting toxicities [within 28 days]

   Part 1 is the 28-day dose escalation part

2. Part 2: Number of participants with dose-limiting toxicities [within 2 years]

   Part 2 is the dose expansion part

3. Parts 1 and 2: Number of participants who experienced an adverse event during the trial [within 2 years]

   Adverse events are collected for the entire duration of study participation

Secondary Outcome Measures

1. Maximum (peak) observed concentration (Cmax) [within 8 days]

   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.

2. Time to maximum observed concentration (Tmax) [within 8 days]

   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.

3. Area under the curve up to the last quantifiable time (AUClast) [within 8 days]

   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.

4. Trough plasma concentration (Ctrough) [within 2 years]

   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

5. Part 2: Number of participants with response to treatment [within 2 years]

   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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02115
2	University of Michigan	Ann Arbor	Michigan	United States	48109
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Duke University	Durham	North Carolina	United States	27710
5	Vanderbilt University	Nashville	Tennessee	United States	37232
6	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT03110354
• Other Study ID Numbers: DS3201-A-U102
• First Posted: Apr 12, 2017
• Last Update Posted: Jun 16, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Daiichi Sankyo, Inc.: AML; ALL; Enhancer of zeste homolog (EZH) inhibitor; DS-3201b
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Study Results

No Results Posted as of Jun 16, 2021