NCT03922100 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: TERMINATED
Registry last update: 2026-03-18

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Rate of Participants Bridged To Hemopoietic Stem Cell Transplantation

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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. * 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. Exclusion Criteria: * 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 * 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Phase 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
intervention Names
Drug: NMS-03592088
label
NMS-03592088
type
EXPERIMENTAL

interventions

arm Group Labels
NMS-03592088
description
Route of administration: Oral
name
NMS-03592088
type
DRUG

Study design

allocation

intervention Model

SEQUENTIAL

intervention 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 Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 63
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
DLTs were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
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)
description
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.
measure
Phase II - Number of Participants Who Achieved Composite Complete Remission (CRc) Rate i.e. Complete Remission (CR) + Complete Remission With Incomplete Hematologic Recovery (CRi).
time Frame
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

description
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.
measure
Treatment-emergent Adverse Events (TEAEs) Graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5.0 Criteria
time Frame
Adverse events were collected from screening visit and assessed up to 18 months
description
Plasma samples were collected and used for pharmacokinetics assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%)
measure
Pharmacokinetic Parameters: Maximum Plasma Concentration (Cmax), Last Measurable Concentration (Clast), and Average Concentration (Cavg) of NMS-03592088
time Frame
Schedule A: Day 1 and Day 21 Schedule B: Day 1 and Day 28
description
Plasma samples were collected and used for pharmacokinetics (PK) assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%)
measure
Pharmacokinetic Parameters: Time to Maximum Plasma Concentration (Tmax), Time to Last Measurable Concentration (Tlast), and Terminal Elimination Half-life (t½,z) of NMS-03592088
time Frame
Schedule A: Day 1 and 21 Schedule B: Day 1 and 28
description
Plasma samples were collected and used for pharmacokinetics (PK) assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%)
measure
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
time Frame
Schedule A: Day 1 and Day 21 Schedule B: Day 1 and Day 28
description
Plasma samples were collected and used for pharmacokinetics (PK) assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%)
measure
Pharmacokinetic Parameters: Apparent Volume of Distribution (V/F) and Apparent Volume of Distribution at Steady State (Vss/F)
time Frame
Schedule A: Day 21
description
Plasma samples were collected and used for pharmacokinetics (PK) assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%)
measure
Pharmacokinetic Parameters: Apparent Plasma Clearance (CL/F) and Apparent Plasma Clearance at Steady State (CLss/F)
time Frame
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
description
Plasma samples were collected and used for pharmacokinetics assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%).
measure
Pharmacokinetic Parameters: Accumulation Ratios (RA) for AUC0-24 and Cmax
time Frame
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.
description
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%)
measure
Pharmacokinetic Parameters: Fraction Excreted Unchanged (FE) of NMS-03592088
time Frame
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.
description
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
measure
Best Response Rate for Participants With Acute Myeloblastic Leukemia (AML).
time Frame
From the date of treatment initiation up to end of study (approximately 1.5 years)
description
Number of participants who achieved a CR as Best Response.
measure
For AML and in Phase II Only: Number of Participants Who Achieved Complete Remission (CR)
time Frame
From the date of first response up to end of study (approximately 1.5 years)
description
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.
measure
For AML and in Phase II Only: Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh) Rate
time Frame
From the date of first response up to end of study (approximately 1.5 years)
description
Defined as the number of participants who achieved CRi or MLFS as best response, divided by the number of participants in the analysis population.
measure
For AML and in Phase II Only: Overall Response Rate (ORR: CRc + CRh + MLFS + PR)
time Frame
From the date of first response up to end of study (approximately 1.5 years)

Full study description

brief 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).

Source references

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice