Study to Assess the Safety, Pharmacokinetics, and Efficacy of AB8939 in patients with Relapsed/Refractory Acute Myeloid Leukemia

Phase 1

• Conditions: Relapsed/Refractory Acute Myeloid Leukemia; MedDRA version: 21.1Level: PTClassification code 10081513Term: Acute myeloid leukaemia refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-005122-28-GR
• Lead Sponsor: AB Science

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-02
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 102

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

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 < 50%), conduction disorder,disorders (Second degree or third-degree atrioventricular block not successfully treated with a pacemaker, Bi-fascicular block), uncontrolled arrythmia, abnormal QT interval (QTcF > 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 < 30 ml/min, or that is not well-controlled and who in the opinion of the principal investigator would impair the ability to assess the safety of AB8939.
14.Patients with history or evidence of neuromuscular or disease such as amyotrophic lateral sclerosis, muscular dystrophy, polymyositis, myasthenia gravis, dermatomyositis, sarcopenia, who in the opinion of the principal investigator would impair the ability to assess the safety of AB8939.
15.Patients with history or evidence of CNS disease such as epilepsy, Alzheimer's and other dementias, strokes, migraine and other headaches possibly related to brain tumor or metastasis, multiple sclerosis, Parkinson's disease, neurological infections, brain tumors, sequellae of head injuries and disorders caused by malnutrition who in the opinion of the principal investigator would impair the ability to assess the safety of AB8939.
16.Patients with diabetes that are not well-controlled by two oral anti-diabetic drugs or insulin and who in the opinion of the principal investigator would impair the ability to assess the safety of AB8939
17. Patients with diabetes, vitamin B12 deficiency, or alcohol addiction
18. Patients with positive test for active AIDS, Hepatitis B, C and tuberculosis
19.Patients with white blood cells count or circulating blasts =20,000 cells/µL with hydroxyurea at screening
20.Patients with:
AST and or ALT = 2.5 ULN,Total bilirubin level > 1.5 ULN (except in case of Gilbert’s syndrome but wit

Study & Design

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

Primary Outcome Measures

Name	Time	Method
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.<br>To assess early efficacy.<br>;Primary end point(s): Rate of dose-limiting toxicity (DLT) ;Timepoint(s) of evaluation of this end point: Day 28

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -PK parameters: Tmax, Cmax, AUC0-t, AUC0-inf, t1/2, Cl, Vd after the first administration for all patients.<br>-Rate of ORR<br>-Rate and durability of CR, CRi, CRMRD-, PR, HI, and MLFS<br>-Response rate based on the subtype of leukemia, risk-status, and genetic abnormalities.;Timepoint(s) of evaluation of this end point: Day 28