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

Nerviano Medical Sciences

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: NMS-03592088

Study type: Interventional

Funder types: Industry

Identifiers

NCT03922100

2018-002793-47 (EudraCT Number)

MKIA-088-001

Details and patient eligibility

About

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).

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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200 participants in 1 patient group

NMS-03592088

Experimental group

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

Treatment:

Drug: NMS-03592088