2024-514018-12-00招募中2 期
Phase-I/II trial for relapsed or refractory AML patients combining cytarabine and mitoxantrone with venetoclax (TUD-RELAX1-070)
Technische Universitaet Dresden9 个研究点 分布在 1 个国家目标入组 55 人开始时间: 2024年10月18日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 55
- 试验地点
- 9
- 主要终点
- Phase I (Escalation part): Maximum tolerated dose of cytarabine in combination with venetoclax plus mitoxantrone in the framework of a 3+3 design
研究概览
简要总结
To determine safety, tolerability, maximum tolerated dose, and recommended phase II dose of venetoclax in combination with increasing cytarabine doses plus fixed dose mitoxantrone in subjects with a relapsed or refractory AML considered fit for intensive salvage therapy.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Signed Informed consent
- •AML according to WHO criteria, excluding APL
- •Relapsed after first or second CR, including relapse after allogeneic stem cell transplantation (dose escalation and expansion phase)
- •Only expansion phase: Primary refractory after 1-2 cycles of standard induction chemotherapy (100 to 200 mg/m2 cytarabine over 7-10 days plus anthracycline or mitoxantrone over 3 days) or equivalent treatment (e.g. CPX351) Note: Primary refractory disease is defined by either ≥ 20% myeloid blasts on early response assessment around day 15 after start of the most recent induction, or by ≥ 5% myeloid blasts after blood count recovery after start of the most recent induction, respectively.
- •Age 18-75 years
- •Fit for intensive chemotherapy, defined by - ECOG 0-2, life expectancy > 3 months - Adequate hepatic function (ALAT/ASAT/Bilirubin ≤2.5 x ULN ) - Adequate renal function assessed by creatinine < 1.5 x ULN OR creatinine clearance (by Cockcroft Gault Formula) ≥ 50 mL/min
- •Patient is afebrile and hemodynamically stable for at least 72 hours at the time of study medication initiation.
- •Male subjects must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 30 days after the last dose of study drug.
- •Women must fulfill at least one of the following criteria in order to be eligible for trial inclusion: o Post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with Serum FSH > 40 U/ml) o Postoperative (i.e. 6 weeks) after bilateral ovariectomy with or without hysterectomy o Women of childbearing potential must have a negative serum pregnancy test performed within 7 days before the first dose of study drug. o Continuous and correct application of a contraception method with a Pearl Index of <1% (e.g. implants, depots, oral contraceptives, intrauterine device – IUD) from time point of signing the informed consent until 30 days after the last dose of study drug. Note: At present, it is not known whether the effectiveness of hormonal contraceptives is reduced by venetoclax. For this reason, women should use a barrier method in addition to hormonal contraceptive methods. o Sexual abstinence o Vasectomy of the sexual partner
排除标准
- •Acute promyelocytic leukemia (AML M3)
- •Cardiovascular disability status of New York Heart Association Class ≥
- •Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
- •Chronic respiratory disease that requires continuous oxygen use.
- •White blood cell count > 25 × 109/L Note: Hydroxyurea is permitted to meet this criterion.
- •AML relapse treatment with any investigational or commercial drug within 14 days before enrolment. Hydroxyurea is allowed until enrolment to control peripheral WBC counts.
- •Substance abuse, medical, psychological, or social conditions that may interfere with the subject’s cooperation with the requirements of the trial or evaluation of the study results
- •Acute non-hematologic toxicities from any prior anti-leukemia therapy or from previous investigational drugs that have not resolved to Grade <2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0
- •History of active or chronic infectious hepatitis unless serology demonstrates clearance of infection (Occult or prior hepatitis B virus (HBV) infection (defined as negative hepatitis B surface antigen and positive total hepatitis B core antibody) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing. Patients who have protective titers of hepatitis B surface antibody after vaccination or prior but cured hepatitis B are eligible. Patients positive for hepatitis C virus antibody are eligible provided PCR is negative for HCV RNA)
- •History of clinically significant liver cirrhosis (e.g., Child-Pugh class B and C).
- •Pregnant or breastfeeding women. Breastfeeding has to be discontinued before onset of and during treatment and should be discontinued for at least 3 months after end of treatment.
- •Live-virus vaccines given within 28 days prior to the initiation of study treatment
- •CNS involvement or subjects with extramedullary disease only
- •Known hypersensitivity to any agent given in association with this study including cytarabine or mitoxantrone
- •Intended hematopoietic stem cell transplantation planned as early conditioning from aplasia without previous blood count recovery
- •Cumulative previous exposure to anthracyclines of >410 mg/m2 doxorubicin equivalents
- •Acute GVHD ≥ grade 2, extensive chronic GVHD or requiring systemic immunosuppressive therapy
- •HIV infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax, as well as anticipated venetoclax mechanism based lymphopenia that may potentially increase the risk of opportunistic infections)
- •Inability to swallow oral medications
- •Any malabsorption condition
结局指标
主要结局
Phase I (Escalation part): Maximum tolerated dose of cytarabine in combination with venetoclax plus mitoxantrone in the framework of a 3+3 design
Phase I (Escalation part): Maximum tolerated dose of cytarabine in combination with venetoclax plus mitoxantrone in the framework of a 3+3 design
Phase II (Expansion part): CR/CRi rate
Phase II (Expansion part): CR/CRi rate
次要结局
未报告次要终点
研究者
Prof. Dr. Christoph Röllig
Scientific
Technische Universitaet Dresden
研究点 (9)
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