A Phase 1/1b Open-Label Study to Determine the Safety and Tolerability of ALRN-6924 Alone and in Combination With Cytarabine (Ara-C) in Patients With Relapsed/Refractory Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome With Wild-Type TP53
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 55
- 主要终点
- Determine maximum tolerated dose (MTD)
研究概览
简要总结
Phase 1/1b, open label, multi-center dose escalation and dose expansion study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 alone or in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia or advanced myelodysplastic syndrome with wild-type (WT) TP53
详细描述
Phase I, open label, multi-center dose escalation (DEP) and dose expansion (EXP) study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 in patients with acute myeloid leukemia or advanced myelodysplastic syndrome with wild-type (WT) TP53. ALRN-6924 is a stabilized cell-permeating peptide designed to disrupt interaction between the p53 tumor suppression protein and its endogenous inhibitors murine double minute 2 (MDM2) and murine double minute X (MDMX)
Men and women 18 years of age and older with relapsed or refractory acute myeloid leukemia or advanced myelodysplastic syndrome and for which standard treatment(s) are not available or are no longer effective can be enrolled. Treatment of patients in the DEP and EXP phases will continue in the study until documentation of disease progression, unacceptable toxicity, or patient or physician decision to discontinue study participation is made.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Relapsed or refractory acute myeloid leukemia or IPSS-R intermediate/high/very high-risk MDS patients
- •Confirmed or anticipated wild-type TP53
- •ECOG (Eastern Cooperative Oncology Group) performance status 0-2
- •Adequate hepatic and renal function
- •Acceptable coagulation function
- •Negative serum or urine pregnancy test within 7 days prior to the first dose of ALRN-6924 for women of child-bearing potential
- •Sufficient wash out from prior therapies and recovery from all significant toxicities
排除标准
- •Patients are eligible for available approved standard therapies
- •Prior treatment with MDM2 inhibitor, with protocol specified exceptions
- •Patients with history of allogeneic stem cell transplantation
- •Leukemic blast counts of >25,000/µl
- •Deletion of chromosome 17, or del(17p)
- •Patients with evidence of current central nervous system leukemic involvement
- •Known hypersensitivity to any study drug component
- •History of coagulopathy
- •Prior specified cardiovascular risk factors
- •Clinically significant gastrointestinal bleeding within 6 months
- •Clinically significant third-space fluid accumulation
- •Pregnant or lactating females
- •Evidence of any serious and/or unstable pre-existing medical condition that would interfere with patient safety ability to provide informed consent
- •Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C
- •Second malignancy within one year, with protocol specified exceptions
研究组 & 干预措施
ALRN-6924
Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days
干预措施: ALRN-6924 (Drug)
ALRN-6924 in combination with cytarabine
Cytarabine (100 or 200 mg/m2) will be administered as an IV infusion followed by ALRN-6924 on Days 1, 8, and 15 every 28 days.
干预措施: ALRN-6924 in combination with cytarabine (Drug)
结局指标
主要结局
Determine maximum tolerated dose (MTD)
时间窗: From the first dose until the end of Cycle 2 (each cycle is 28 days)
Determine the dose limiting toxicities (DLT) and the maximum tolerated dose (MTD) or the optimal biological dose (OBD) of ALRN-6924 in adult patients with AML or MDS
Evaluate the safety and tolerability of ALRN-6924 alone and in combination with cytarabine
时间窗: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
次要结局
- Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)(First 2 cycles (each cycle is 28 days))
- Determine immunogenicity of ALRN-6924(Approximately 16 weeks)
- Determine best overall response, duration of response, morphologic leukemia-free state, leukemia free survival, percentage of MDA patients who have achieved hematologic improvement, changes in transfusion rate and early death rate(Approximately 16 weeks)