Study of experimental drug NMS-03592088 in combination with azacitidine in adult patients with blood malignancies

Phase 1

• Conditions: Acute Myeloid Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML); MedDRA version: 21.0Level: LLTClassification code 10028552Term: Myeloid leukaemia, acuteSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-005013-14-IT
• Lead Sponsor: ERVIANO MEDICAL SCIENCES SR

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-10-12
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1.Patients with confirmed diagnosis of de novo or secondary AML as defined by the 2017 ELN recommendations (Dohner H et al., Blood, Jan 2017) positive for FLT3 ITD and/or TKD point mutations in the BM or PB as determined by the local standard test performed at study entry. Patients with an allelic frequency = or > 5 % as determined by local laboratories will be considered to have FLT3-ITD positive disease.
•Patients must be refractory to at least 1 cycle of induction chemotherapy or relapsed after achieving remission with a prior intensive treatment which may include HSCT. Patients must have received = or < 3 prior therapeutic regimens. Treatments given only for cytoreductive purposes (e.g. hydroxyurea) do not count as prior therapeutic regimen. Patients who received the combination of AZA and a FLT3 inhibitor as last regimen prior to study entry are excluded.
•Patients deemed unfit for intensive induction chemotherapy or unsuitable or unwilling to receive standard therapy due to age, comorbidities or other factors. Patients must have received no more than 1 prior therapeutic regimen and the regimen should not include the combination of AZA and a FLT3 inhibitor. Treatments given only for cytoreductive purposes (e.g. hydroxyurea) do not count as prior therapeutic regimen.
2.Patients with confirmed diagnosis of CMML, as defined by WHO criteria. Patients who have received prior AZA are eligible if the treating physician feels that participation to the study is in the best patients' interest.
3. Adult (age = or > 18 years) patients.
4.ECOG performance status < or = 2.
5.In the absence of rapidly progressing disease, the interval from prior antitumor treatment to time of study drugs administration should be at least 2 weeks for any agents other than hydroxyurea.
6.All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTCAE version 5.0 Grade < or = 1, unless there is evidence of rapidly progressive disease.
7.Adequate hepatic function, as defined by serum transaminases (i.e., AST/ALT) < or = 2.5 x ULN, ALP < or = 2.5 x ULN and total bilirubin < or = 1.5 x ULN unless abnormality considered due to Gilbert’s syndrome.
8.Adequate renal function, as defined by the estimated glomerular filtration rate (eGFR) = or > 60 mL/min as calculated by the BSA-unadjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
9.Patients must use highly effective contraception or abstinence. Female patients of childbearing potential must agree to the use of highly effective contraception or abstinence 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 highly effective contraception or abstinence during the period of therapy and in the following 90 days after discontinuation of study treatment.
10.Capability to swallow capsules intact (without chewing, crushing, or opening)
11.Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study indications or procedures
12.Signed and dated IEC or IRB-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.
Are the trial subjects under 18? no
Number of subjects f

Exclusion Criteria

1.Current enrollment in another interventional clinical study
2.Diagnosis of acute pro-myelocytic leukemia or 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 = or > 2 related to the transplant
6.Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressive treatment
7.Patients with QTcF interval = or > 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 should 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 components of the NMS-03592088 drug product or AZA 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.Known active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection requiring systemic treatment.
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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified