2023-505259-39-00招募中2 期
A phase 1/2a, first-in-human, open-label, multicenter, dose escalation study of MP0533 in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 221
- 试验地点
- 7
- 主要终点
- Incidence of CRS and non-CRS DLTs during the first cycle of treatment (phase 1 only)
研究概览
简要总结
Investigating MP0533 as monotherapy in patients with R/R AML and MDS/AML is to:
- Determine the safety and tolerability
- Define the recommended phase 2 dose regimen (RP2D-R) and/or the maximum tolerated dose-regimen (MTD-R) (phase 1 only)
- Evaluate the preliminary anti-leukemic activity (primary for phase 2a, secondary for phase 1)
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
- 是
入选标准
- •Has signed and dated written informed consent prior to performing any study procedure, including screening
- •Diagnosis of relapsed/refractory AML or relapsed/refractory MDS/AML according to the ELN recommendation 2022
- •Age ≥18 years old on the day of signing informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
- •Anticipated life expectancy ≥ 12 weeks by investigator judgement
- •Adequate renal and hepatic function: a. Creatinine clearance > 40 mL/min on the basis of Cockcroft-Gault glomerular filtration rate estimation, unless considered AML- or MDS-related b. Serum bilirubin ≤ 2.5 x upper limit of normal (ULN), unless considered AML- or MDS-related or due to Gilbert’s syndrome c. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN, unless considered AML- or MDS-related
- •White blood count (WBC) ≤ 15G/L at day of trial drug infusion (prior hydroxyurea allowed)
- •Is using highly effective contraception, for females of childbearing potential (FCBP) and for men.
排除标准
- •Mixed phenotype acute leukemia
- •Major surgery within 28 days prior to start of study medication
- •Other malignancy requiring active therapy, but adjuvant endocrine therapy is allowed
- •Left ventricular ejection fraction of < 50% on echocardiographic exam at screening
- •Any uncontrolled active infection
- •Treatment with investigational agents or agents targeting CD33, CD123 or CD70 within 4 weeks or five times the half-life of the agent, whichever is longer, prior to start of trial medication
- •History or evidence of clinically significant cardiovascular disease defined as at least one of the following criteria: Evidence of poorly controlled arterial hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg); Myocardial infarction or unstable angina pectoris within 6 months before screening; Heart failure (New York Heart Association Class III or IV); Any cardiac arrhythmia that is not well controlled; QT corrected (QTc) prolongation ≥ Grade 2 (> 480 ms) at screening measured on 2 separate electrocardiograms (ECG) at least 10 minutes apart; Clinically significant valvular heart disease
- •Pulmonary disease with clinically relevant hypoxia (need for continuous oxygen inhalation)
- •Known Human Immunodeficiency Virus (HIV)-infected patients who are healthy and have a low risk of Acquired Immunodeficiency Syndrome (AIDS)-related outcomes are eligible, if: No history of AIDS-defining opportunistic infection within past 12 months; Patient agrees to concomitant antiretroviral therapy (ART) if not currently on ART, is on ART for ˃ 4 weeks and has a HIV viral load ˂ 400 copies/mL
- •Active hepatitis.
- •Any vaccines within 28 days before first study drug administration
- •Allogeneic HCT within the last 3 months prior to start of trial medication and/or eligibility for standard 2nd line of targeted therapy, like gilteritinib for FLT3 mutated AML, unless this therapeutic option has already been given and proven ineffective (patient relapsed or resistant to), or contraindicated, or confounding mutations exist, or there is a lack of access to this recommended therapy.
- •History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥ 2 years before screening and of relatively low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of residual disease; Adequately treated carcinoma in situ without evidence of disease; Cancer patients with incidental histologic findings of prostate cancer that, in the opinion of the investigator, is not deemed to require active therapy may be eligible, pending discussion and approval by the Sponsor
- •Concurrent enrollment in another clinical trial, unless it is an observational (noninterventional) study or it is the follow-up period of an interventional study
- •Patients with favorable AML mutations according to ELN recommendation 2022 and
- •More than 2 prior lines of anti-leukemic therapy.
- •Known hypersensitivity to any of the excipients of the investigational medicinal product (IMP), i.e. finished MP0533 drug
- •Any condition that, in the opinion of the investigator, would interfere with evaluation of the IMP or interpretation of the patient’s data
- •Unable or unwilling to comply with all study requirements for clinical visits, examinations, tests and procedures, and contraception requirements
- •Patient deprived of liberty by a judicial or administrative decision, patient admitted to a social institution or who is under a measure of legal protection, patient hospitalized without consent or who is in an emergency
- •Active GvHD requiring immune-suppressive therapy (other than prednisone (or equivalent) ≤ 10mg/d)
- •Use of immunosuppressive drugs (other than prednisone (or equivalent) ≤10mg/d) in the past 4 weeks
- •Clinical signs of AML in the central nervous system
结局指标
主要结局
Incidence of CRS and non-CRS DLTs during the first cycle of treatment (phase 1 only)
Incidence of CRS and non-CRS DLTs during the first cycle of treatment (phase 1 only)
Type, incidence and severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Type, incidence and severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Changes in laboratory safety parameters and vital signs
Changes in laboratory safety parameters and vital signs
Overall response rate (ORR) based on best overall response of complete remission, complete remission with partial hematological recovery (CRh); complete remission with incomplete hematological recovery (CRi), morphologic leukemia-free state (MLFS) and partial remission (PR) according to the European LeukemiaNet (ELN) response criteria 2022 (phase 2a only)
Overall response rate (ORR) based on best overall response of complete remission, complete remission with partial hematological recovery (CRh); complete remission with incomplete hematological recovery (CRi), morphologic leukemia-free state (MLFS) and partial remission (PR) according to the European LeukemiaNet (ELN) response criteria 2022 (phase 2a only)
次要结局
- Determination of PK parameters including (but not limited to) Cmax, time at Cmax (Tmax), minimal serum concentration (Cmin), area under the concentration-time curve (AUC), total CL, volume of distribution (Vd) and t1/2
- Different levels of CR, CRh, Cri, MLFS and PR according to the ELN response criteria 2022, separately and pooled
- Event free survival (EFS) based on ELN response criteria 2022
- Duration of response (DoR) based on ELN response criteria 2022
- Overall survival (OS) (phase 2a only)
- Number of patients proceeding to a stem cell transplantation (phase 2a only)
- Transfusion-Independence (TI)
研究者
Medical Monitor
Scientific
Molecular Partners AG
研究点 (7)
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