Acute Myeloid LeukemiaPhase 1NCT03671564

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

A Phase 1 study testing Milademetan in people with Acute Myeloid Leukemia, run by Daiichi Sankyo Co., Ltd. at 8 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 20 years and older
Conditions the study is for: Acute Myeloid Leukemia
What is being tested?: Milademetan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 8 sitesJapan
Study dates: 23 Aug 2018to 11 Sep 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

Japan8 sites

Japanese Red Cross Narita Hospital
Chiba, 286-0041
Kyusyu University Hospital
Fukuoka, 812-8582
Gifu Municipal Hospital
Gifu, 500-8513
Chugoku Central Hospital
Hiroshima, 720-0001
National Hospital Organization Kumamoto Medical Center
Kumamoto, 860-0008
Tenri Hospital
Nara, 632-8552
NTT Medical Center Tokyo
Tokyo, 141-8625
National Hospital Organization Disaster Medical Center
Tokyo, 190-0014

Other trials in Japan

About this study

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

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
Being tested: Milademetan
Keywords: Oncology, MDM2, Escalation with overdose control (EWOC)
Medical subject headings: Leukemia, Myeloid, Acute, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MilademetanDrug
Also called DS-3032b
Milademetan was administered orally once daily on Days 1 to 14 in a 28-day cycle.

Study groups in NCT03671564
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Drug: Milademetan

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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
Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.
Measured: 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
Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis.
Measured: 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
AUC during 8 hours (AUC8h), AUC during 24 hours (AUC24h), AUC up to the last quantifiable concentration (AUClast), and AUC up to infinity (AUCinf) are presented for Day 1 of Cycle 1 and were assessed using non-compartmental analysis. AUC8h for Day 14 of Cycle 1 is also presented.
Measured: 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
Terminal elimination half-life (T1/2) was assessed using non-compartmental analysis.
Measured: 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
Trough plasma concentration (Ctrough) was assessed using non-compartmental analysis.
Measured: Day 14 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)
Number of Participants With Best Response Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Best response was defined as the best measured response over all response assessments (complete remission [CR], CR with incomplete hematological recovery [CRi], CR with partial hematological recovery [CRh], partial remission [PR], morphologic leukemia-free state [MLFS], stable disease [SD], or progressive disease [PD]) at all time points after the start of study treatment. The best response will be SD if the response is assessed as SD three or more times consecutively in the protocol-specified evaluation of the antitumor effect. If the response is not assessed as SD three or more times consecutively, the best response will be Not Applicable (unconfirmed SD).
Measured: From the start of study treatment to the end of study treatment, up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Aug 201811 Sep 2019

First posted14 Sep 2018
Study start23 Aug 2018
Primary completion11 Sep 2019
Study completion11 Sep 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03671564
Sponsor's protocol ID: DS3032-A-J104
Other IDs: 184054
Status last verified: Jan 2023
First submitted: 4 Sep 2018
Last updated: 7 Nov 2023
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
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All Acute Myeloid Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03671564
Acronym / sponsor ID: DS3032-A-J104
Conditions: Acute Myeloid Leukemia
Keywords: Oncology, MDM2, Escalation with overdose control (EWOC)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 14 participants (actual)
Lead sponsor: Daiichi Sankyo Co., Ltd.Industry (pharma, biotech, devices)
Study start: 23 Aug 2018 (actual)
Primary completion: 11 Sep 2019 (actual)
Study completion: 11 Sep 2019 (actual)
First posted: 14 Sep 2018 (actual)
Results: Posted 7 Nov 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Milademetan (90 mg/Day)	Experimental	Drug: MilademetanParticipants who received milademetan 90 mg daily (QD) Day 1 - 14 followed by 14-day rest in a 28-day cycle.
Milademetan (120 mg/Day)	Experimental	Drug: MilademetanParticipants who received milademetan 120 mg daily (QD) Day 1 - 14 followed by 14-day rest in a 28-day cycle.
Milademetan (160 mg/Day)	Experimental	Drug: MilademetanParticipants who received milademetan 160 mg daily (QD) Day 1 - 14 followed by 14-day rest in a 28-day cycle.

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (3 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MilademetanAlso: DS-3032bMilademetan was administered orally once daily on Days 1 to 14 in a 28-day cycle.	Drug	Milademetan (120 mg/Day), Milademetan (160 mg/Day), Milademetan (90 mg/Day)

Primary outcome

Number of Participants With Dose Limiting Toxicities (DLTs) Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Time frame: First 28 Days of Cycle 1
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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Time frame: From date of signing of informed consent form up to 30 days after last dose of study drug, up to 1 year
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.

6 secondary outcomes

Maximum Plasma Concentration (Cmax) of Milademetan Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 14 of Cycle 1: Pre-dose and 1, 2, 3, 6, and 8 hours post-dose (each cycle is 28 days)
Number of Participants With Best Response Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Time frame: From the start of study treatment to the end of study treatment, up to 1 year

Results and safety

Results posted to the registry on 7 Nov 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Milademetan (90 mg/Day)	4	0
Milademetan (120 mg/Day)	6	0
Milademetan (160 mg/Day)	4	0

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

Time frame: First 28 Days of Cycle 1. Count of participants. Unit: Participants

Measure	Milademetan (90 mg/Day) n = 4	Milademetan (120 mg/Day) n = 3	Milademetan (160 mg/Day) n = 4
Value	0	0	0

Population analysed: Dose-limiting toxicities were assessed in the DLT Evaluable Set. 3 participants in the 120-mg cohort were excluded from analysis because study treatment was discontinued before completion of the DLT evaluation period.

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

Time frame: From date of signing of informed consent form up to 30 days after last dose of study drug, up to 1 year. Count of participants. Unit: Participants

Measure	Milademetan (90 mg/Day) n = 4	Milademetan (120 mg/Day) n = 6	Milademetan (160 mg/Day) n = 4
Value	4	5	4

Population analysed: Treatment-emergent adverse events were assessed in the Safety Analysis Set.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AE) were collected from the date of signing the informed consent form up to 30 days after last dose of the study drug, up to 1 year.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Milademetan (90 mg/Day)	2 of 4 (50%)	4 of 4 (100%)	0 of 4
Milademetan (120 mg/Day)	2 of 6 (33.3%)	5 of 6 (83.3%)	0 of 6
Milademetan (160 mg/Day)	0 of 4 (0%)	4 of 4 (100%)	0 of 4

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Related trials for Acute Myeloid Leukemia

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A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
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RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Study Leader study director

Daiichi Sankyo

8 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Milademetan in people with Acute Myeloid Leukemia, run by Daiichi Sankyo Co., Ltd. at 8 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (DLTs) Following Administration of Milademetan in Participants With Relapsed or Refractory Acute Myeloid Leukemia (time frame: First 28 Days of Cycle 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03671564.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2023.