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

NCT03922100 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: MKIA-088-0012018-002793-47
• Study Type: interventional
• Target: 63
• Locations: 3 countries
• Sites: 11

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).

Conditions

Acute Myeloid Leukemia (AML); Chronic Myelomonocytic Leukemia (CMML)

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

  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)

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

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

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

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

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

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

• 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

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

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

  Schedule A: Day 21

Study Arms (1)

NMS-03592088

EXPERIMENTAL

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

Drug: NMS-03592088

Interventions

NMS-03592088 DRUG

Route of administration: Oral

NMS-03592088

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Nerviano Medical Sciences: lead

Study Sites (11)

Centre Hospitalier du Mans

Le Mans, 72037, France

Location

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

Nantes, 44000, France

Location

CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque

Pessac, 33604, France

Location

Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

Location

ASST Papa Giovanni XXIII

Bergamo, BG, 24127, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, MI, 20162, Italy

Location

Istituto Clinico Humanitas

Rozzano, MI, 20089, Italy

Location

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

Bologna, 40138, Italy

Location

ASST Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Study stopped due to strategic reasons. The decision was 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.

Results Point of Contact

• Title: Lisa Mahnke
• Organization: Nerviano Medical Sciences S.r.l.

clinicaltrials@nervianoms.com

+39 0331-581111

Study Officials

• Alessandro Rambaldi, MD

  ASST Papa Giovanni XXIII

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: April 19, 2019
• Study Start: April 3, 2019
• Primary Completion: August 29, 2024
• Study Completion: August 29, 2024
• Last Updated: March 18, 2026
• Results First Posted: March 18, 2026

Record last verified: 2026-02

Locations

IT (6); ES (1); FR (4)