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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03922100
Other study ID # MKIA-088-001
Secondary ID 2018-002793-47
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date April 3, 2019
Est. completion date February 28, 2026

Study information

Verified date February 2024
Source Nerviano Medical Sciences
Contact Anders Elm Pedersen
Phone +39 0331-581111
Email clinicaltrials@nervianoms.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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).


Recruitment information / eligibility

Status Recruiting
Enrollment 200
Est. completion date February 28, 2026
Est. primary completion date December 28, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
NMS-03592088
Route of administration: Oral

Locations

Country Name City State
France Centre Hospitalier du Mans Le Mans
France Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu Nantes
France Hôpital Saint-Antoine Paris
France CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque Pessac
France Centre Hospitalier Lyon-Sud Pierre-Bénite
Italy ASST Papa Giovanni XXIII Bergamo BG
Italy Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi Bologna
Italy ASST Spedali Civili di Brescia Brescia
Italy Azienda Ospedaliero-Universitaria Careggi Firenze
Italy ASST Grande Ospedale Metropolitano Niguarda Milano MI
Italy Fondazione IRCCS Policlinico San Matteo Pavia
Italy Fondazione Policlinico Universitario Agostino Gemelli Roma
Italy Istituto Clinico Humanitas Rozzano MI
Italy Ospedale Le Molinette Torino
Spain Catalan Institute of Oncology (ICO) Badalona
Spain Hospital San Pedro de Alcántara Cáceres
Spain Hospital Universitari i Politècnic La Fe Valencia

Sponsors (1)

Lead Sponsor Collaborator
Nerviano Medical Sciences

Countries where clinical trial is conducted

France,  Italy,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Phase I - Number of Participants with drug related first-cycle dose limiting toxicities (DLTs) DLTs will be classified according to NCI CTCAE version 5.0. From the date of treatment initiation up to end of Cycle 1 (each Cycle is 28 days)
Primary Phase II FLT3-ITD mut AML: Composite Complete Remission (CRc) Rate Defined by the 2022 European LeukemiaNet (ELN) recommendations. From the date of treatment initiation up to end of study (approximately 1.5 years)
Secondary Number of participants with Adverse Events (AEs) Safety will be assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.). From the Informed Consent signature to 28 days after the last on-study treatment administration.
Secondary Maximum plasma concentration (Cmax) of NMS-03592088 and its metabolites NMS-03593860 and NMS-03603422: Plasma samples will be collected and used for pharmacokinetics assessments. Phase 1 Dose Escalation and Dose Expansion Schedule A: Cycle 1 and Cycle 2 various timepoints; Phase 1 Dose Escalation Schedule B: Cycle 1, 2 and 3 various timepoints; Phase 1 Backfill Cycle 1 and Cycle 2 various timepoints (Each Cycle is 28 days)
Secondary Time to maximum plasma concentration (Tmax) of NMS-03592088 and its metabolites NMS-03593860 and NMS-03603422: Plasma samples will be collected and used for pharmacokinetics assessments. Phase 1 Dose Escalation and Dose Expansion Schedule A: Cycle 1 and Cycle 2 various timepoints; Phase 1 Dose Escalation Schedule B: Cycle 1, 2 and 3 various timepoints; Phase 1 Backfill Cycle 1 and Cycle 2 various timepoints (Each Cycle is 28 days)
Secondary Area under the plasma concentration versus time curve (AUC)] of NMS-03592088 and its metabolites NMS-03593860 and NMS-03603422: area under the plasma concentration versus time curve (AUC)] Plasma samples will be collected and used for pharmacokinetics assessments. Phase 1 Dose Escalation and Dose Expansion Schedule A: Cycle 1 and Cycle 2 various timepoints; Phase 1 Dose Escalation Schedule B: Cycle 1, 2 and 3 various timepoints; Phase 1 Backfill Cycle 1 and Cycle 2 various timepoints (Each Cycle is 28 days)
Secondary Renal clearance of NMS-03592088 and its metabolites NMS-03593860 and NMS-03603422 excreted in urine (only Phase I) Timepoints up to 24-hours post dose
Secondary Fraction of NMS-03592088 and its metabolites NMS-03593860 and NMS-03603422 excreted in urine (only Phase I) Timepoints up to 24-hours post dose
Secondary Best response rate for participants with AML Number and percentage of participants with CR, CRi, CRh, PR, MLFS, SD, No Response and Progressive Disease (PD). From the date of treatment initiation up to end of study (approximately 1.5 years)
Secondary Best response rate for participants with CMML Number and percentage of participants with CR, CCR, PR, MR, CB and PD. From the date of treatment initiation up to end of study (approximately 1.5 years)
Secondary Overall Survival (OS) OS is defined as the time from the date of the first dose of study drug until the date of death for any cause. From the date of treatment initiation until death or up to 1.5 years from patient's first dose, whichever comes first
Secondary Time to Response (TTR) TTR is defined as the time from the first dose of study drug until the date of first response (CRc or PR). From the date of treatment initiation up to end of study (approximately 1.5 years)
Secondary Duration of Response (DoR) Duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse of any type for participants who achieved CRc or PR. From the date of first response up to end of study (approximately 1.5 years)
Secondary Event-Free Survival (EFS) For patients with diagnosis of AML the primary analysis measures the time from the date of treatment initiation to the date of first documentation of disease progression or hematologic relapse after CR/CRh/CRi, treatment failure or death from any cause, whichever comes first.
For patients with CMML, EFS will be defined as the time from treatment start until disease progression, relapse after CR, CCR, PR, MR or CB, treatment failure, or death from any cause, whichever comes first.
From the date of treatment initiation until death or up to 1.5 years from patient's first dose, whichever comes first
Secondary Relapse-free Survival (RFS) For patients with diagnosis of AML in the primary analysis it is measured only for patients achieving CR or CRi, and it is defined as the time from the date of first achievement of a CR/CRi until the date of relapse or death from any cause.
For patients with CMML diagnosis, RFS will be measured from the date of first achievement of CR, CCR, PR, MR or CB until the date of relapse or death from any cause.
From the date of treatment initiation until death or up to 1.5 years from patient's first dose, whichever comes first
Secondary For AML and in Phase II only: Complete Remission (CR) Rate Defined as the number of patients who achieve a CR as Best Response, divided by the number of participants in the analysis population. From the date of first response up to end of study (approximately 1.5 years)
Secondary For AML and in Phase II only: Complete Remission and Complete Remission with Partial Hematologic Recovery (CR/CRh) Rate Defined as the number of patients who achieve a CR or CRh or CRi as best response, divided by the number of participants in the analysis population. From the date of first response up to end of study (approximately 1.5 years)
Secondary For AML and in Phase II only: Overall Response Rate (ORR: CRc + CRh + MLFS + PR) Defined as the number of participants who achieve CR, CRi, CRh, MLFS or PR as best response, divided by the number of participants in the analysis population. From the date of first response up to end of study (approximately 1.5 years)
Secondary Rate of conversion from transfusion-dependence to transfusion-independence Defined as the proportion of participants being post-baseline transfusion independent from baseline transfusion dependence. From the date of first response up to end of study (approximately 1.5 years)
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