Clinical trial NCT03671564: Study of Milademetan in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Official title: Phase 1, Open-label, Dose Escalation Study of Milademetan, an Oral MDM2 Inhibitor, to Assess Safety, Tolerability and Pharmacokinetics in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: Oncology
MDM2
Escalation with overdose control (EWOC)
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2018-09-14
Enrollment: 14
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
timeFrame: First 28 Days of Cycle 1
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
timeFrame: From date of signing of informed consent form up to 30 days after last dose of study drug, up to 1 year
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
timeFrame: Days 1 & 14 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
timeFrame: Days 1 & 14 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
timeFrame: Days 1 & 14 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)
measure: Terminal Elimination Half-Life (T1/2) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
timeFrame: Day 1 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)
measure: Trough Plasma Concentration (Ctrough) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
timeFrame: Day 14 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)
measure: Number of Participants With Best Response Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
timeFrame: From the start of study treatment to the end of study treatment, up to 1 year
Other outcomes:
Locations:
city: Chiba
country: Japan
facility: Japanese Red Cross Narita Hospital
city: Fukuoka
country: Japan
facility: Kyusyu University Hospital
city: Gifu
country: Japan
facility: Gifu Municipal Hospital
city: Hiroshima
country: Japan
facility: Chugoku Central Hospital
city: Kumamoto
country: Japan
facility: National Hospital Organization Kumamoto Medical Center
city: Nara
country: Japan
facility: Tenri Hospital
city: Tokyo
country: Japan
facility: NTT Medical Center Tokyo
city: Tokyo
country: Japan
facility: National Hospital Organization Disaster Medical Center
Study officials:
affiliation: Daiichi Sankyo
name: Clinical Study Leader
role: STUDY_DIRECTOR
References: