临床试验/2024-516641-39-00

2024-516641-39-00招募中2 期

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

Ab Science16 个研究点分布在 4 个国家目标入组 60 人开始时间: 2024年12月2日最近更新: 2025年6月16日

适应症

试验速览

阶段: 2 期
状态: 招募中
发起方
入组人数: 60
试验地点: 16
主要终点: Rate of dose-limiting toxicity (DLT)

研究概览入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

研究设计

研究类型: Interventional

入排标准

年龄范围: 18 years 至 65+ years（18-64 Years, 65+ Years）
接受健康志愿者: 否

入选标准

•Patients with documented diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) based on the last version of the World Health Organization classification.
•Patients must have adequate organ function without severe heart, lung, liver, kidney or nervous system dysfunction or immune deficiency
•In the absence of rapidly progressing disease, the interval from prior treatment to time of AB8939 administration should be at least 14 days.
•Patients are able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
•Adequate recovery, to a maximum of Grade 1 (CTCAE V5.0) from toxicity of prior therapy.
•Patients are able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
•Patients are able and willing to comply with trial procedures as per protocol, including bone marrow biopsies
•Patients are able and willing to comply with trial procedures as per protocol, including bone marrow biopsies
•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
•All patients should have white blood cell count <25 × 109 /l prior to initiation of venetoclax and cytoreduction prior to treatment may be required
•Patients must be expected to complete the treatment period, in the opinion of the investigator.
•In the absence of rapidly progressing disease, the interval from prior treatment to time of AB8939 administration should be at least 14 days.
•Male or non-pregnant female ≥ 18 years old at the time of signing the informed consent.
•ECOG performance status ≤ 1
•Patients must have adequate organ function without severe heart, lung, liver, kidney or nervous system dysfunction or immune deficiency
•Patients not eligible to hematopoietic stem cell transplantation (HSCT) at the time of inclusion
•Expansion cohort trial: Patients not eligible to hematopoietic stem cell transplantation (HSCT) at the time of inclusion
•Adequate recovery, to at a maximum of Grade 1 (CTCAE version5.0) from toxicity of prior therapy.
•EXPANSION COHORT TRIAL -Patients with a documented diagnosis of acute myeloid leukemia (AML) based on the last version of the World Health Organization classification.
•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 patients were not eligible to high dose chemotherapy in first line. 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
•All patients should have white blood cell count <25 × 109 /l prior to initiation of venetoclax and cytoreduction prior to treatment may be required
•Patients must be expected to complete the treatment period, in the opinion of the investigator.
•Male or non-pregnant female ≥ 18 years old at the time of signing the informed consent.
•ECOG performance status ≤ 2

排除标准

•Patients eligible to hematopoietic stem cell transplantation (HSCT) at the time of inclusion
•Patients with clinically active CNS leukemia
•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
•Women who are lactating/breastfeeding or who plan to breastfeed while on trial
•Patients with major surgery within 28 days prior to the first administration of AB8939
•Patients with radiation therapy within 28 days prior to the first administration of AB8939
•Patients with uncontrolled hypertension e.g. SBP/DBP >149/90 mmHg despite two anti-hypertensive therapy
•Patients with history or evidence of neuromuscular disease such as amyotrophic lateral sclerosis, muscular dystrophy, polymyositis, myasthenia gravis, dermatomyositis, sarcopenia,
•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
•Patients with history or evidence of renal disease such as severe renal failure defined as creatinine clearance < 30 ml/min,
•Patients with history or evidence of neuromuscular disease such as amyotrophic lateral sclerosis, muscular dystrophy, polymyositis, myasthenia gravis, dermatomyositis, sarcopenia,
•Patients with major surgery within 28 days prior to the first administration of AB8939
•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
•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%
•Patients with vitamin B12 deficiency, or alcohol addiction
•Women with a positive pregnancy test
•Patients with positive test for active AIDS (HIV1-2 test), Hepatitis B (antigene HBs), C (PCR positive), and tuberculosis
•Patients with white blood cells count or circulating blasts ≥ 20,000 cells/µL with hydroxyurea at screening
•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)
•Women who are lactating/breastfeeding or who plan to breastfeed while on trial
•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.
•Women with a positive pregnancy test
•Patients with radiation therapy within 28 days prior to the first administration of AB8939
•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
•Women planning to become pregnant while on study and 6months after receiving the last dose of study drug
•Patients under psychiatric or, protected by law under guardianship or curatorship, or in emergency situations or, prisoners or, without National Health Insurance
•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%
•Patients diagnosed with acute promyelocytic leukemia (M3)
•Patients with vitamin B12 deficiency, or alcohol addiction
•Patients with positive test for active AIDS (HIV1-2 test), Hepatitis B (antigene HBs), C (PCR positive), and tuberculosis
•Patients with white blood cells count or circulating blasts ≥ 20,000 cells/µL with hydroxyurea at screening
•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
•Patients eligible to standard of care
•Patients with history or evidence of renal disease such as severe renal failure defined as creatinine clearance < 30 ml/min,
•Patients with HSCT within 100 days prior to the first administration of AB8939
•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.
•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
•Expansion Cohort Trial: Patients eligible to standard of care
•Patients with HSCT within 100 days prior to the first administration of AB8939
•Men and women of reproductive potential who are unwilling to practice a highly effective method(s) of birth control while on trial and 6 months for women and 3 months for men; after receiving the last dose of study drug
•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
•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
•Women planning to become pregnant while on study and 6months after receiving the last dose of study drug
•Patients under psychiatric or, protected by law under guardianship or curatorship, or in emergency situations or, prisoners or, without National Health Insurance
•Patients with known toxicity to venetoclax and/or to azacitidine who intend to participate in steps involving either venetoclax or/and azacitidine
•Patients with clinically active CNS leukemia
•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
•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
•Patients with uncontrolled hypertension e.g. SBP/DBP >149/90 mmHg despite two anti-hypertensive therapy.
•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
另有 3 项未显示

结局指标

主要结局

Rate of dose-limiting toxicity (DLT)

次要结局

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

研究者

发起方

Ab Science

申办方类型

Pharmaceutical company

责任方

Principal Investigator

主要研究者

Christian Fassotte

Scientific

Ab Science

研究点 (16)

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