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

• Status: Recruiting
• Trial end date: 2023-09-30
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to explore safety, tolerability, including the maximum tolerated dose, and antitumor activity of NMS-03592088 in adult patients with relapsed or refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nerviano Medical Sciences

Criteria

Inclusion Criteria:

Phase I:

1. 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 2017 European LeukemiaNet (ELN) recommendations

• CMML as defined by the World Health Organization (WHO) criteria.

Phase II:

2. Cohort 1 (FLT3 mut AML):

• Patients with confirmed diagnosis of AML as defined by the 2017 ELN recommendations positive for FLT3 internal tandem duplication (ITD) and/or tyrosine kinase domain (TKD) point mutations in the bone marrow (BM) or peripheral blood (PB) as determined by the local standard test performed at study entry. Patients with an allelic frequency ≥10% will be considered to have FLT3-ITD-mutated disease.

• Patients must be refractory to at least 1 cycle of induction chemotherapy or relapsed after achieving remission with a prior therapy or unsuitable to receive standard therapy due to age, comorbidities or other factors.

• Prior treatment with a FLT3 inhibitor is allowed.

3. Cohort 2 (CMML):

• Patients with confirmed diagnosis of CMML, as defined by WHO criteria who have failed previous therapies or are unsuitable to receive standard therapy due to age, comorbidities or other factors.

Applying to both Phase I and Phase II:

4. Adult (age > or = 18 years) patients

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

6. The interval from prior antitumor treatment to time of NMS-03592088 administration should be at least 2 weeks for any agents other than hydroxyurea.

7. All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTCAE version 5.0 Grade ≤1

8. Adequate hepatic function.

9. Adequate renal function.

10. Patients must use effective contraception. Female patients must be surgically sterile or be postmenopausal, or must agree to the use of effective contraception during the period of therapy and in the following 90 days after discontinuation of study treatment. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy and in the following 90 days after discontinuation of study treatment.

11. Capability to swallow capsules intact (without chewing, crushing, or opening)

12. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study indications or procedures

13. Signed and dated Institutional Review Board/Ethic Committee (IRB/EC)-approved informed consent form indicating that the patient is aware of the neoplastic nature of his/her disease and has been informed of the procedures to be followed, the investigational nature of the therapy, potential benefits, side effects, discomforts, risks and alternative treatments.

Exclusion Criteria:

1. Current enrollment in another interventional clinical study

2. Diagnosis of acute promyelocytic leukemia or breakpoint cluster region-Abelson (BCR-ABL)-positive leukemia

3. 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.

4. Patients with known leukemia involvement of CNS

5. Hematopoietic stem cell transplantation (HSCT) within 3 months of treatment start and/or persistent non-hematologic toxicities of Grade ≥2 related to the transplant.

6. Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressive treatment

7. Patients with QTcF interval ≥ 480 milliseconds or with risk factors for torsade de pointes (e.g., uncontrolled heart failure, uncontrolled hypokalemia, history of prolonged QTc interval or family history of long QT syndrome). For patients receiving treatment with concomitant medications known to prolong the QTc interval, replacement with another treatment needs to be considered. If replacement or discontinuation is not clinically feasible, a careful risk/benefit evaluation should be performed prior to enrollment.

8. Pregnancy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the screening period prior to start of study drug.

9. Breast-feeding or planning to breast feed during the study or within 3 months after study treatment.

10. Known hypersensitivity to any of the components of the NMS-03592088 drug product.

11. 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

12. Known active, life threatening or clinically significant uncontrolled systemic infection.

13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness

14. Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) C infection.

15. Known active gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.

16. Known active gastrointestinal ulcer

17. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.