HM2024-29: Phase I/II Clinical Trial of Proteasome Inhibitor in Combination With CPX-351 for the Treatment of Newly-Diagnosed TP53-mutated Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Percentage of Participants with Complete Response
研究概览
简要总结
This is a Phase I/II study evaluating safety and efficacy of proteasome inhibitor (bortezomib) in combination with CPX-351 (liposomal daunorubicin and cytarabine) for the treatment of newly-diagnosed TP53-mutated acute myeloid leukemia (TP53m AML).
The primary endpoint of the study is to define safety/tolerability (phase I) and preliminary efficacy profile (phase II) of the treatment. The secondary endpoints of interest are complete remission (CR) rate, detectable minimal residual disease (MRD) status, overall response rate (ORR), rate of allogeneic hematopoietic cell transplantation (allo-HCT), treatment-related mortality (TRM), overall survival (OS), achievement of complete remission anytime in 1 year, and disease-free survival (DFS) at 1 year and 2 years. All the patient outcomes assessments will be performed as part of standard-of-care AML management.
The hypothesis is the combination of bortezomib and CPX-351 will have an acceptable safety profile in this patient population based on the data from previous studies. The treatment will attenuate Nuclear Factor kB pathway activation in these cells and eradicate TP53m leukemia stem cells (LSC) leading to increased response rate and survival in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult (age ≥ 18 years at time of consent)
- •Have not received any systemic chemotherapy for the treatment of AML. Use of hydroxyurea and leukapheresis to control excess peripheral blasts is permissible. WBC < 25,000 to initiate bortezomib, must reach this threshold by day 7 of CPX-
- •Karnofsky performance status (KPS) ≥ 70
- •Adequate renal, hepatic and cardiac function defined as
- •Renal: An estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2
- •Hepatic: AST and ALT ≤3 x ULN, ALP ≤2.5 x ULN, and total bilirubin ≤1.5 x ULN. (exception for Gilbert's syndrome or leukemic infiltration of liver)
- •Cardiac: New York Heart Association (NYHA) Class I or II, left ventricular ejection fraction > 50% by echocardiogram, MUGA or cardiac MRI
- •Sexually active couples of childbearing potential must agree to use effective contraception or abstinence during treatment and for at least 7 months after the final dose of study drug
- •Provides voluntary written consent before the performance of any study related activities not part of standard of care.
排除标准
- •Received systemic chemotherapy for the treatment of AML
- •Bi-phenotypic acute leukemia or mixed lineage leukemia, acute promyelocytic leukemia
- •Active central nervous system malignancy or symptoms of CNS involvement
- •Symptomatic extramedullary disease
- •Known history of uncontrolled HIV or active hepatitis B or active hepatitis C infection
- •Has any of the following cardiac abnormalities
- •Symptomatic congestive heart failure
- •Myocardial infarction less than or equal to 6 months prior to enrollment
- •Unstable angina pectoris
- •Serious uncontrolled cardiac arrhythmia
- •Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Potential participants with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g., cervix) may enroll irrespective of the time of diagnosis
- •Participants for whom administration of CPX-351 would exceed their lifetime cumulative daunorubicin exposure limit of 550 mg/m2 (or 400 mg/m2 in patients with prior chest radiation) or equivalent anthracycline dose.
- •Pregnant or breastfeeding, or planning pregnancy within 3 months after the treatment completion
研究组 & 干预措施
Phase 1: Dose Level 2
Bortezomib 1mg/m2 in combination with CPX-351
干预措施: Bortezomib (Drug)
Phase 1: Dose Level 2
Bortezomib 1mg/m2 in combination with CPX-351
干预措施: CPX-351 (Drug)
Phase 1: Dose Level 3
Bortezomib 1.3 mg/m2 in combination with CPX-351
干预措施: Bortezomib (Drug)
Phase 1: Dose Level -1
Bortezomib 0.7mg/m2 in combination with CPX-351
干预措施: Bortezomib (Drug)
Phase 1: Dose Level -1
Bortezomib 0.7mg/m2 in combination with CPX-351
干预措施: CPX-351 (Drug)
Phase 1: Dose Level 3
Bortezomib 1.3 mg/m2 in combination with CPX-351
干预措施: CPX-351 (Drug)
Phase 1: Dose Level 4
Bortezomib 1.5 mg/m2 in combination with CPX-351
干预措施: Bortezomib (Drug)
Phase 1: Dose Level 4
Bortezomib 1.5 mg/m2 in combination with CPX-351
干预措施: CPX-351 (Drug)
Phase 2
Maximum tolerated dose of Bortezomib in combination with CPX-351
干预措施: Bortezomib (Drug)
Phase 2
Maximum tolerated dose of Bortezomib in combination with CPX-351
干预措施: CPX-351 (Drug)
结局指标
主要结局
Percentage of Participants with Complete Response
时间窗: 2 years
To evaluate the CR rate of bortezomib + CPX-351 for the treatment of TP53m AML.
Determine Maximum Tolerated Dose
时间窗: 1 year
次要结局
- Determine Overall Response Rate(2 years)
- Average rate of allo-HCT among participants(2 years)
- Overall Survival(2 year)
- Average time to relapse(2 year)
- Overall Survival(1 year)