Overview
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).
Principal investigator
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
* 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
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