A Phase I/II Study of Venetoclax and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 38
- 试验地点
- 5
- 主要终点
- Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225
研究概览
简要总结
The study is a multicenter, open label Phase I/II trial.
- To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 added to venetoclax for patients with CD33 positive relapsed/refractory AML. (Phase 1 portion)
- To assess the percentage of patients with CR, CRh, or Overall Response (CR + CRh), up to 6 months after the start of treatment without receiving other AML therapies. (Phase 2 portion)
详细描述
The study is a multicenter, open label Phase I and Phase II trial combining lintuzumab-Ac225 with venetoclax in patients who have relapsed or refractory AML.
The Phase I portion is a dose-finding study which will enroll at least three patients at each dose level. Patients in a dose level will be observed for a minimum of 4 weeks before dose escalation occurs. There is no dose escalation for any individual patient.
The Phase II portion of the study will enroll patients at the MTD dose level of lintuzumab-Ac225 as determined in the Phase I portion of the study. The goal of the Phase II portion will be to further characterize the safety and efficacy of the MTD dose of lintuzumab-Ac225.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Refractory or relapsed AML which will include:
- •Refractory disease will be defined as at least 1 prior treatment with no remission.
- •Relapsed disease will be defined as 5% or more blasts in bone marrow seen after remission.
- •Patients with AML arising from myelodysplastic syndromes (including CMML) or myeloproliferative neoplasms (secondary AML, ts-AML) are also eligible.
- •Circulating blast count ≤ 200/μL within 10 days prior to first cycle of treatment. Hydroxyurea should be used to keep the peripheral blast count ≤ 200/μL until the first day of protocol treatment, to the extent that this is possible
- •Estimated creatinine clearance ≥ 50 mL/min
- •AST and ALT ≤ 3.0 x ULN
- •Bilirubin ≤ 3.0 x ULN
排除标准
- •Active CNS Leukemia.
- •Known HIV infection or known hepatitis B or hepatitis C infection (with a detectable viral load).
- •Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
- •Secondary refractory AML (e.g., treated for current relapse without achieving remission);
- •a. With the exception that single agent FLT3 inhibitors, IDH1/IDH2 inhibitors are allowed for current relapse without achieving remission.
- •Have received prior radiation to maximally tolerated levels to any critical normal organ.
- •Clinically significant cardiac disease.
- •Active, uncontrolled serious infection.
- •Have other non-myeloid malignancy within 2 years of entry (with exceptions).
- •Psychiatric disorder that would preclude study participation
- •Previous solid organ transplant (prior treatment with SCT is allowed but not if patient has GVHD or is still receiving immunosuppression/GVHD therapy).
研究组 & 干预措施
Phase I and Phase II
Lintuzumab-Ac225 administered on Day 5 of each cycle for four cycles (unless in the 0.5 μCi/kg or 0.25 μCi/kg cohorts, where there is a potential for an additional four cycles, pending PI and Medical Monitor review).
Venetoclax taken on Days 1-21 of each cycle for up to 12 cycles.
Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery.
干预措施: Spironolactone (Drug)
Phase I and Phase II
Lintuzumab-Ac225 administered on Day 5 of each cycle for four cycles (unless in the 0.5 μCi/kg or 0.25 μCi/kg cohorts, where there is a potential for an additional four cycles, pending PI and Medical Monitor review).
Venetoclax taken on Days 1-21 of each cycle for up to 12 cycles.
Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery.
干预措施: Lintuzumab-Ac225 (Biological)
Phase I and Phase II
Lintuzumab-Ac225 administered on Day 5 of each cycle for four cycles (unless in the 0.5 μCi/kg or 0.25 μCi/kg cohorts, where there is a potential for an additional four cycles, pending PI and Medical Monitor review).
Venetoclax taken on Days 1-21 of each cycle for up to 12 cycles.
Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225
时间窗: Cycle 1, up to 48 days
To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 added to venetoclax for patients with CD33 positive relapse/refractory AML.
Phase II: Overall Response (CR + CRh + CRi)
时间窗: Up to 6 months
To assess the percentage of patients with CR, CRh, CRi or Overall Response (CR + CRh + CRi), up to 6 months after the start of treatment without receiving other AML therapies.
次要结局
- Phase I and II: Evaluate incidence of AEs and SAEs(Through study completion, up to 2 years)
- Phase I: Overall Response(Up to 6 months)
- Phase I and II: OS(End of 6 months, 12 months, 2 years)
- Phase I and II: DFS(End of 6 months, 12 months, 2 years)
- Phase I and II: Evaluate BH3 priming assay results(Completion of Cycle 1, estimated 1 month)
- Phase I and II: MRD status(From date of first dose until the date of first documented response, first assessment at 6 months)
- Phase I and II: Lab abnormalities (other than hematologic indices)(Through study completion, up to 2 years)