Relapsed/Refractory Acute Myeloid Leukemia MedDRA version: 21.1 Level: PT Classification code 10081513 Term: Acute myeloid leukaemia refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: 1-{4-[2-(5-ethoxymethyl-2-methyl-phenylamino)-oxazol-5-yl]-phenyl}-imidazolidin-2-one
Product Code: AB8939
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed IN
Sponsors
AB Science
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with documented diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) based on the last version of the World Health Organization classification 2. AML patients in second or third line of treatment, if they were eligible to high dose chemotherapy in first line. Or AML patients in second line of treatment, if they were not eligible to high dose chemotherapy in first line Or MDS patients in second or third line of treatment, and with high risk at prognostic based on the IPSS-R scoring system. A line of treatment is defined as a combination of treatments that ends by a progression of the disease or toxicity related to this treatment 3. Patients not eligible to hematopoietic stem cell transplantation (HSCT) at the time of inclusion 4. Patients must be expected to complete the treatment period in the opinion of the investigator 5. Male or non-pregnant female = 18 years old at the time of signing the informed consent 6. ECOG performance status = 1 7. Patients must have adequate organ function without severe heart, lung, liver, kidney or nervous system dysfunction or immune deficiency 8. In the absence of rapidly progressing disease, the interval from prior treatment to time of AB8939 administration should be at least 14 days 9. Adequate recovery, to a maximum of Grade 1 (CTCAE v5.0) from toxicity of prior therapy 10. Patients are able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures 11. Patients are able and willing to comply with study procedures as per protocol, including bone marrow biopsies Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 82 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Patients eligible to a standard of care 2. Patients eligible to hematopoietic stem cell transplantation (HSCT) at the time of inclusion 3. Patients diagnosed with acute promyelocytic leukemia (M3) 4. Patients with clinically active CNS leukemia 5. Patients with other active malignancies are ineligible unless they have been disease-free for at least three years and are deemed by the investigator to be at low risk for recurrence or progression of that malignancy 6. Patients with major surgery within 28 days prior to the first administration of AB8939 7. Patients with radiation therapy within 28 days prior to the first administration of AB8939 8. Patients with HSCT within 100 days prior to the first administration of AB8939 9. Patients who have received prior standard treatment within 2 weeks or those who have not recovered from adverse events due to treatment administered more than 2 weeks earlier. 10. Patients who are receiving any other investigational administered with the intention to treat their malignancy within 2 weeks from the last dose prior to entering the study, with the exception of hydroxyurea. 11. Patients with uncontrolled hypertension e.g. SBP/DBP >149/90 mmHg despite two anti-hypertensive therapy. 12. Patients with history or evidence of cardiovascular disease such as stroke, ischemic heart disease, (myocardial infarction, acute coronary syndrome, unstable angina), heart failure, (EF 450 ms for male and >470 ms for female patients), history of torsades de pointes, pericarditis, valvular disease that are not well-controlled and who in the opinion of the principal investigator would impair the ability to assess the safety of AB8939 13. Patients with history or evidence of renal, disease such as severe renal failure defined as creatinine clearance 1.5 ULN (except in case of Gilbert’s syndrome but wit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To define the safety and tolerability of AB8939 in patients with refractory or relapsed AML and MDS by determining the dose-limiting toxicities, the maximum tolerated dose (MTD) and the recommended dose for dose expansion study.;Secondary Objective: To determine the pharmacokinetic profile in the function of dose. To assess early efficacy. ;Primary end point(s): Rate of dose-limiting toxicity (DLT) ;Timepoint(s) of evaluation of this end point: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -PK parameters: Tmax, Cmax, AUC0-t, AUC0-inf, t1/2, Cl, Vd after the first administration for all patients. -Rate of ORR -Rate and durability of CR, CRi, CRMRD-, PR, HI, and MLFS -Response rate based on the subtype of leukemia, risk-status, and genetic abnormalities.;Timepoint(s) of evaluation of this end point: Day 28 | — |
Countries
Canada, France, Greece, Italy, Spain, United States
Contacts
Public ContactCEO
AB Science
Outcome results
None listed