Study of Milademetan in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

NCT03671564 | Completed Phase 1 Results

• 2 other identifiers: DS3032-A-J104184054
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 8

Brief Summary

This is a Phase 1, multicenter, open-label study to evaluate safety, tolerability and pharmacokinetics of milademetan in Japanese patients with relapsed or refractory acute myeloid leukemia. The milademetan initial dose will be Level 1: 90 mg. No increase in the milademetan dose will be made in the same participant. Dose-limiting toxicity associated with milademetan occurring at each level will be assessed, and the maximum tolerated dose (MTD) will be decided using a modified continuous reassessment method (mCRM).

Conditions

Acute Myeloid Leukemia

Keywords

Oncology; MDM2; Escalation with overdose control (EWOC)

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLTs) Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  A dose limiting toxicities (DLTs) is defined as any Grade 3 or higher non-hematological adverse event unless related to the primary disease, course of the primary disease, complications, or concomitant medications, that occurs during the DLT evaluation period (28 days of Cycle 1). The following events will be assessed as DLTs: Grade 4 aspartate aminotransferase (AST)/alanine aminotransferase (ALT), Grade 3 AST/ALT lasting ≥3 days, Grade 3 AST/ALT with Grade ≥2 total bilirubin, and unable to complete at least 75% of the prescribed doses of milademetan in Cycle1 (28 days) as a result of Grade ≥2 events.

  First 28 Days of Cycle 1

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs after the first administration, or that worsens relative to the pre-treatment state. An AE is any untoward or unintended sign, symptom, or disease noted in participants who received the study drug, whether it is considered to be related to the study drug or not.

  From date of signing of informed consent form up to 30 days after last dose of study drug, up to 1 year

Secondary Outcomes (6)

• Maximum Plasma Concentration (Cmax) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Days 1 & 14 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)

• Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Days 1 & 14 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)

• Area Under the Plasma Concentration-Time Curve (AUC) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Days 1 & 14 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)

• Terminal Elimination Half-Life (T1/2) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Day 1 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)

• Trough Plasma Concentration (Ctrough) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Day 14 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)

Study Arms (3)

Milademetan (90 mg/Day)

EXPERIMENTAL

Participants who received milademetan 90 mg daily (QD) Day 1 - 14 followed by 14-day rest in a 28-day cycle.

Drug: Milademetan

Milademetan (120 mg/Day)

EXPERIMENTAL

Participants who received milademetan 120 mg daily (QD) Day 1 - 14 followed by 14-day rest in a 28-day cycle.

Drug: Milademetan

Milademetan (160 mg/Day)

EXPERIMENTAL

Participants who received milademetan 160 mg daily (QD) Day 1 - 14 followed by 14-day rest in a 28-day cycle.

Drug: Milademetan

Interventions

Milademetan DRUG

Milademetan was administered orally once daily on Days 1 to 14 in a 28-day cycle.

Also known as: DS-3032b

Milademetan (120 mg/Day); Milademetan (160 mg/Day); Milademetan (90 mg/Day)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed or refractory AML
• AML for which no standard treatment is available
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2

You may not qualify if:

• Acute Promyelocytic Leukemia
• Chronic myelogenous leukemia in blast crisis (BCR-ABL fusion gene positive)
• Presence of central nervous system involvement of leukemia or a history of primary central nervous system leukemia

Sponsors & Collaborators

• Daiichi Sankyo Co., Ltd.: lead

Study Sites (8)

Japanese Red Cross Narita Hospital

Chiba, 286-0041, Japan

Location

Kyusyu University Hospital

Fukuoka, 812-8582, Japan

Location

Gifu Municipal Hospital

Gifu, 500-8513, Japan

Location

Chugoku Central Hospital

Hiroshima, 720-0001, Japan

Location

National Hospital Organization Kumamoto Medical Center

Kumamoto, 860-0008, Japan

Location

Tenri Hospital

Nara, 632-8552, Japan

Location

NTT Medical Center Tokyo

Tokyo, 141-8625, Japan

Location

National Hospital Organization Disaster Medical Center

Tokyo, 190-0014, Japan

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasms

Interventions

milademetan

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Clinical Director
• Organization: Daiichi Sankyo, Inc.

CTRinfo@dsi.com

908-992-6400

Study Officials

• Clinical Study Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: September 14, 2018
• Study Start: August 23, 2018
• Primary Completion: September 11, 2019
• Study Completion: September 11, 2019
• Last Updated: November 7, 2023
• Results First Posted: November 7, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

JP (8)