A Phase 1/2 Study to Assess the Safety, Pharmacokinetics, and Efficacy of Daily Intravenous of AB8939 in patients with Relapsed/Refractory Acute Myeloid Leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ab Science

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

2 Dec 2024 → ongoing

Decision date (initial)

2024-12-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

AB Science

External identifiers

EU CT number

2024-516641-39-00

EudraCT number

2020-005122-28

WHO UTN

U1111-1310-9293

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

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 trial.

Secondary objectives 2

1. To determine the pharmacokinetics profile in function of dose.
2. To assess early efficacy.

Conditions and MedDRA coding

Acute Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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. Patients must have adequate organ function without severe heart, lung, liver, kidney or nervous system dysfunction or immune deficiency
3. In the absence of rapidly progressing disease, the interval from prior treatment to time of AB8939 administration should be at least 14 days.
4. Patients are able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
5. Adequate recovery, to a maximum of Grade 1 (CTCAE V5.0) from toxicity of prior therapy.
6. Patients are able and willing to comply with trial procedures as per protocol, including bone marrow biopsies
7. AML patients in second, third, fourth, or fifth 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, third, fourth, or fifth line of treatment and with high risk at prognostic based on the IPSS-R scoring system.
8. All patients should have white blood cell count <25 × 109 /l prior to initiation of venetoclax and cytoreduction prior to treatment may be required
9. Patients must be expected to complete the treatment period, in the opinion of the investigator.
10. Male or non-pregnant female ≥ 18 years old at the time of signing the informed consent.
11. ECOG performance status ≤ 1
12. Patients not eligible to hematopoietic stem cell transplantation (HSCT) at the time of inclusion

Exclusion criteria 27

1. Patients eligible to hematopoietic stem cell transplantation (HSCT) at the time of inclusion
2. Patients with clinically active CNS leukemia
3. Patients with other active malignancies are ineligible unless they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence or progression of that malignancy
4. Women who are lactating/breastfeeding or who plan to breastfeed while on trial
5. Patients with major surgery within 28 days prior to the first administration of AB8939
6. Patients with radiation therapy within 28 days prior to the first administration of AB8939
7. Patients with uncontrolled hypertension e.g. SBP/DBP >149/90 mmHg despite two anti-hypertensive therapy
8. Patients with history or evidence of neuromuscular disease such as amyotrophic lateral sclerosis, muscular dystrophy, polymyositis, myasthenia gravis, dermatomyositis, sarcopenia,
9. 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 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
10. Patients with history or evidence of renal disease such as severe renal failure defined as creatinine clearance < 30 ml/min,
11. 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
12. Patients with diabetes that are not well-controlled by two oral anti-diabetic drugs or insulin with Fasting Blood Glycemia > 110mg/dl and /or HbA1c >7%
13. Patients with vitamin B12 deficiency, or alcohol addiction
14. Women with a positive pregnancy test
15. Patients with positive test for active AIDS (HIV1-2 test), Hepatitis B (antigene HBs), C (PCR positive), and tuberculosis
16. Patients with white blood cells count or circulating blasts ≥ 20,000 cells/µL with hydroxyurea at screening
17. Patients with AST and or ALT ≥ 2.5 ULN,Total bilirubin level > 1.5 ULN (except in case of Gilbert’s syndrome but within the limit of 3 x ULN) Serum creatinine ≥ 1.5 ULN and Albumin <30g/l (as AB8939 has a strong plasma protein binding)
18. Men and women of reproductive potential who are unwilling to practice a highly effective method(s) of birth control while on study and 6months for women and 3 months for men; after receiving the last dose of study drug
19. Women planning to become pregnant while on study and 6months after receiving the last dose of study drug
20. Patients under psychiatric or, protected by law under guardianship or curatorship, or in emergency situations or, prisoners or, without National Health Insurance
21. Patients diagnosed with acute promyelocytic leukemia (M3)
22. Patients eligible to standard of care
23. Patients with HSCT within 100 days prior to the first administration of AB8939
24. 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.
25. Patients likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge
26. Patients with known toxicity to venetoclax and/or to azacitidine who intend to participate in steps involving either venetoclax or/and azacitidine
27. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of dose-limiting toxicity (DLT)

Secondary endpoints 4

1. Rate and duration of composite response rate (CRc) is defined as CRc = CR + CRh + CRi + CRp
2. Rate of ORR
3. PK parameters: Tmax, Cmax, AUC0-t, AUC0-inf, t1/2, Cl, Vd, after the first administration for all patients
4. Response rate based on the subtype of leukemia, risk-status, and genetic abnormalities

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ab Science

Sponsor organisation

Ab Science

Address

3 Avenue George V

City

Paris

Postcode

75008

Country

France

Scientific contact point

Organisation

Ab Science

Contact name

Christian Fassotte

Public contact point

Organisation

Ab Science

Contact name

Alain Moussy

Third parties 1

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

Corrective measures 2 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications