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Acute Myeloid Leukemia (AML)Phase 1/2NCT03922100

Study of NMS-03592088 in Patients With Relapsed or Refractory AML or CMML

A Phase 1/2 study testing NMS-03592088 in people with Acute Myeloid Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML), run by Nerviano Medical Sciences at 11 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to explore safety, tolerability, including the maximum tolerated dose and the recommended Phase II dose (RP2D), and antitumor activity of NMS-03592088 in adult patients with relapsed or refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
NMS-03592088
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
11 sitesin 3 countries
Study dates
3 Apr 2019to 29 Aug 2024
Phase
Phase 1/2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with relapsed/refractory disease who have failed standard therapy or are unsuitable for standard treatment, with one the following confirmed diagnosis: AML as defined by the European LeukemiaNet (ELN)
  • Patients with confirmed diagnosis of AML as defined by the 2022 ELN recommendations
  • Patients must have failed standard of care.
  • Adult (age ≥ 18 years) patients
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • The interval from prior antitumor treatment to time of NMS-03592088 administration should be at least 2 weeks for any agents other than hydroxyurea.
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  • All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTCAE version 5.0 Grade ≤1
  • Adequate hepatic and renal function
  • Patients must use highly effective contraception.
  • Signed and dated IEC or IRB-approved informed consent form.

Who cannot join

  • Current enrollment in another interventional clinical study
  • Diagnosis of acute promyelocytic leukemia or Breakpoint cluster region-Abelson (BCR-ABL)-positive leukaemia
  • Currently active second malignancy, except for adequately treated basal or squamous cell skin cancer and/or cone biopsied in situ carcinoma of the cervix uteri and/or superficial bladder cancer.
  • Patients with known leukemia involvement of central nervous system (CNS)
  • Hematopoietic stem cell transplantation (HSCT) within 3 months of treatment start and/or persistent non-hematologic toxicities of Grade ≥2 related to the transplant
  • Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressive treatment
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  • Patients with QTcF interval ≥ 480 milliseconds or with risk factors for torsade de pointes
  • Pregnancy.
  • Breast-feeding or planning to breast feed during the study or within 3 months after study treatment.
  • Any of the following in the previous 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis
  • Known active, life threatening or clinically significant uncontrolled systemic infection.
  • Known active gastrointestinal disease
  • Known active gastrointestinal ulcer
  • Other severe or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.
  • Known diagnosis of myasthenia gravis
  • US only:
  • Signs or symptoms of myasthenia gravis or stroke during screening
  • Patients with myasthenia gravis specific autoantibodies or any known history of myasthenia gravis (MG) autoantibodies at screening window
  • Concomitant medications with the potential to cause de novo myasthenia gravis, worsening of myasthenia gravis or cause myasthenia gravis-like symptoms
  • Uncontrolled hypertension, atrial fibrillation or flutter, ventricular arrhythmia or receiving treatment for cardiac rhythm disorder or diabetes that is not adequately controlled
  • Other protocol specific inclusion/exclusion criteria may apply

Trial locations and contacts

11 sites in 3 countries.

11 sites in 3 countries

Italy6 sites
  • ASST Papa Giovanni XXIII

    Bergamo, BG, 24127

  • Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

    Bologna, 40138

  • ASST Spedali Civili di Brescia

    Brescia, 25123

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, MI, 20162

  • Fondazione Policlinico Universitario Agostino Gemelli

    Roma, 00168

  • Istituto Clinico Humanitas

    Rozzano, MI, 20089

Other trials in Italy

France4 sites
  • Centre Hospitalier du Mans

    Le Mans, 72037

  • Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu

    Nantes, 44000

  • CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque

    Pessac, 33604

  • Centre Hospitalier Lyon-Sud

    Pierre-Bénite, 69495

Other trials in France

Spain1 site
  • Hospital Universitari i Politècnic La Fe

    Valencia, 46026

Other trials in Spain

About this study

Official title: A Phase I/II Study of NMS-03592088, a FLT3, KIT and CSF1R Inhibitor, in Patients With Relapsed or Refractory AML or CMML

The purpose of this study is to explore safety, tolerability, including the maximum tolerated dose and the recommended Phase II dose (RP2D), and antitumor activity of NMS-03592088 in adult patients with relapsed or refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML).

Being tested
NMS-03592088
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic

What participants receive

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

  • NMS-03592088Drug

    Route of administration: Oral

Study groups in NCT03922100
Study groupRoleWhat they receive
NMS-03592088ExperimentalPhase I Dose Escalation * Schedule A - Starting dose of 20 mg/day * Schedule B - Starting dose of 120 mg/day Only one dose level open for enrollment except EU backfill cohorts. Phase II Dose Expansion (Exploratory) - (EU) Recommended Phase II Dose (RP2D) of NMS-03592088 in Phase 1 * Cohort 1: Patients who have failed standard of care including venetoclax and gilteritinib based therapies * Cohort 2: Patients who have failed standard of care
Receives: Drug: NMS-03592088

What is being measured

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

  1. Phase I - Number of Participants With Drug Related First-cycle Dose Limiting Toxicities (DLTs)

    DLTs were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Measured: From screening to end of first 28-days cycle (47 months)

  2. Phase II - Number of Participants Who Achieved Composite Complete Remission (CRc) Rate i.e. Complete Remission (CR) + Complete Remission With Incomplete Hematologic Recovery (CRi).

    CR = complete remission; CRc = composite complete remission rate; CRh = complete remission with partial hematologic recovery, CRi = complete remission with incomplete hematologic recovery; MLFS = morphologic leukemia free state; ORR = overall response rate; SD = stable disease Categories defined by the 2022 European LeukemiaNet (ELN) recommendations.

    Measured: At Screening; Day 1 of Cycle 2 and Cycle 3; and Day 1 at subsequent even cycle; up to End of Treatment visit (within 7 days of the final dose of study drug), up to 17 months

Secondary outcomes (13)
  1. Treatment-emergent Adverse Events (TEAEs) Graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5.0 Criteria

    TEAE with maximum Common Terminology Criteria (CTC) grade (graded by NCI CTCAE Version 5.0) experienced by each participant is presented. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented here. Phase 2 started before Phase 1 completed.

    Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living.

    Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.

    Grade 4 Life-threatening consequences; urgent intervention indicated.

    Measured: Adverse events were collected from screening visit and assessed up to 18 months

  2. Pharmacokinetic Parameters: Maximum Plasma Concentration (Cmax), Last Measurable Concentration (Clast), and Average Concentration (Cavg) of NMS-03592088

    Plasma samples were collected and used for pharmacokinetics assessments.

    Mean values of PK parameters are presented with the coefficient of variation (CV%)

    Measured: Schedule A: Day 1 and Day 21 Schedule B: Day 1 and Day 28

  3. Pharmacokinetic Parameters: Time to Maximum Plasma Concentration (Tmax), Time to Last Measurable Concentration (Tlast), and Terminal Elimination Half-life (t½,z) of NMS-03592088

    Plasma samples were collected and used for pharmacokinetics (PK) assessments.

    Mean values of PK parameters are presented with the coefficient of variation (CV%)

    Measured: Schedule A: Day 1 and 21 Schedule B: Day 1 and 28

  4. Pharmacokinetic Parameter: Area Under the Concentration-time Curve to the Last Measurable Concentration (AUClast) and Area Under the Concentration-time Curve From Time Zero to 24 Hour (AUC0-24) of NMS-03592088

    Plasma samples were collected and used for pharmacokinetics (PK) assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%)

    Measured: Schedule A: Day 1 and Day 21 Schedule B: Day 1 and Day 28

  5. Pharmacokinetic Parameters: Apparent Volume of Distribution (V/F) and Apparent Volume of Distribution at Steady State (Vss/F)

    Plasma samples were collected and used for pharmacokinetics (PK) assessments.

    Mean values of PK parameters are presented with the coefficient of variation (CV%)

    Measured: Schedule A: Day 21

  6. Pharmacokinetic Parameters: Apparent Plasma Clearance (CL/F) and Apparent Plasma Clearance at Steady State (CLss/F)

    Plasma samples were collected and used for pharmacokinetics (PK) assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%)

    Measured: Schedule A: Day 1 and Day 21 Schedule B: Day 1 and Day 28 CL/F: Evaluation of CL/F for Day 1 of all arms in Schedule A and Schedule B and Day 28 of Schedule B has not been performed

  7. Pharmacokinetic Parameters: Accumulation Ratios (RA) for AUC0-24 and Cmax

    Plasma samples were collected and used for pharmacokinetics assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%).

    Measured: Schedule A: Day 21 Schedule B: Day 28 Evaluation of Accumulation ratios (RA) for AUC0-24 and Cmax on Day 1 of all arms in Schedule A and Schedule B has not been performed.

  8. Pharmacokinetic Parameters: Fraction Excreted Unchanged (FE) of NMS-03592088

    Urine samples were collected and used for pharmacokinetics (PK) assessments. Only cohorts with available data are presented. The assessment was performed only during the Phase I of the study.

    Mean values of PK parameters are presented with the coefficient of variation (CV%)

    Measured: Schedule A: Day 21 Schedule B: Day 28 Evaluation of Fraction excreted unchanged (FE) for Arms 20, 40, 80, 120 and 180 mg of Schedule A and Arm 360+150 mg of Schedule B has not been performed.

  9. Best Response Rate for Participants With Acute Myeloblastic Leukemia (AML).

    For participants with AML diagnosis the number and percentage of participants with best response achieved on treatment in the following categories: CR, CRi, CRh, PR, MLFS, SD, No Response and Progressive Disease (PD).

    CR= complete response; CRh= Complete Remission with Partial Hematologic Recovery, CRi= Complete Remission with Incomplete Hematologic Recovery; CRc= Complete Remission Rate; MLFS= Morphologic leukemia free state; ORR= Overall Response Rate; PR= Partial Remission; SD= Stable Disease

    Measured: From the date of treatment initiation up to end of study (approximately 1.5 years)

  10. For AML and in Phase II Only: Number of Participants Who Achieved Complete Remission (CR)

    Number of participants who achieved a CR as Best Response.

    Measured: From the date of first response up to end of study (approximately 1.5 years)

  11. For AML and in Phase II Only: Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh) Rate

    Defined as the number of participants who achieved a CR or CRh or CRi as best response, divided by the number of participants in the analysis population.

    Measured: From the date of first response up to end of study (approximately 1.5 years)

  12. For AML and in Phase II Only: Overall Response Rate (ORR: CRc + CRh + MLFS + PR)

    Defined as the number of participants who achieved CRi or MLFS as best response, divided by the number of participants in the analysis population.

    Measured: From the date of first response up to end of study (approximately 1.5 years)

  13. Rate of Participants Bridged To Hemopoietic Stem Cell Transplantation

    Defined as proportion of participants bridged to hemopoietic stem cell transplantation

    Measured: From the date of first response up to end of study (approximately 1.5 years)

Timeline

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

  1. First posted19 Apr 2019
  2. Study start3 Apr 2019
  3. Primary completion29 Aug 2024
  4. Study completion29 Aug 2024

Why it stopped: Study stopped due to strategic reasons. The decision is not based on specific safety findings as the safety observed in the phase II part of the study is in line with what was reported in the phase I part.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
This is an open-label Phase I/II, first-in-human (FIH), non-randomized, multi-center study conducted in two parts: a Phase I including patients with AML and CMML and a Phase II exploratory study comprising two parallel cohorts of AML FLT3 mutated patients. The Phase II portion of the study is currently being conducted in EU only.
Masking
None (open label)
Enrolment
63 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03922100
Sponsor's protocol ID
MKIA-088-001
Other IDs
2018-002793-47, 2018
Status last verified
Feb 2026
First submitted
4 Apr 2019
Last updated
18 Mar 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NMS-03592088 in people with Acute Myeloid Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML), run by Nerviano Medical Sciences at 11 sites in 3 countries.

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 10 inclusion and 21 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: stopped early, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Italy, France, Spain. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 18 Mar 2026). 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?

Phase I - Number of Participants With Drug Related First-cycle Dose Limiting Toxicities (DLTs) (time frame: From screening to end of first 28-days cycle (47 months)). 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?
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 18 Mar 2026.

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