A Phase I/II Study of Venetoclax and Azacitidine and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Phase II: Overall Response (CR + CRh + CRi + MLFS)
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 when given in combination with venetoclax and azacitidine for patients with CD33 positive AML. (Phase I portion)
- To assess the percentage of patients with CR, CRh, CRi, MLFS or Overall Response (CR + CRh + CRi + MLFS), 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 and azacitidine 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 each dose level will be observed for a minimum of 4 weeks before dose escalation occurs. There is no dose escalation for any individual patient. Lintuzumab-Ac225 is administered on Day 8 of the first 4 treatment cycles.
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
- •Histologically confirmed acute myeloid leukemia
- •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.
- •White blood cell (WBC) count < 10 x 109/L;
- •a. Use of hydroxyurea, prior to Cycle 1 and during Cycles 1 and 2, is permitted to lower the WBC count in the peripheral blood.
- •Age > 18 years.
- •Estimated creatinine clearance ≥ 50 mL/min calculated by the Cockroft-Gault formula.
- •AST and ALT ≤ 3.0 x ULN (unless considered to be due to leukemic organ involvement).
- •Bilirubin ≤ 3.0 x ULN (unless considered to be due to leukemic organ involvement).
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
排除标准
- •Have acute promyelocytic leukemia (APL).
- •Active CNS leukemia. Patients with symptoms of CNS involvement, particularly those with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to exclude CNS disease. Symptoms include cranial neuropathies, other neurologic deficits, and headache.
- •Have received prior radiation to maximally tolerated levels to any critical normal organ.
- •Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
- •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 as GVHD or is still receiving immunosuppression/GVHD therapy).
研究组 & 干预措施
Phase I and Phase II
Lintuzumab-Ac225 will be administered on Day 8 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 will be taken on Days 1-21 of each cycle for up to 12 cycles.
Azacitidine will be administered on Days 1-7 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 will be administered on Day 8 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 will be taken on Days 1-21 of each cycle for up to 12 cycles.
Azacitidine will be administered on Days 1-7 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)
Phase I and Phase II
Lintuzumab-Ac225 will be administered on Day 8 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 will be taken on Days 1-21 of each cycle for up to 12 cycles.
Azacitidine will be administered on Days 1-7 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: Azacitidine (Drug)
结局指标
主要结局
Phase II: Overall Response (CR + CRh + CRi + MLFS)
时间窗: Up to 6 months
To assess the percentage of patients achieving CR, CRh, CRi, morphologic leukemia-free state (MLFS), or Overall Response (CR + CRh + CRi + MLFS), up to 6 months after the start of treatment without receiving other AML therapies
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 when given in combination with venetoclax and azacitidine for patients with CD33 positive AML
次要结局
- Phase I and II: Lab abnormalities (other than hematologic indices)(Through study completion, up to 2 years)
- Phase I: Overall Response(Up to 6 months)
- 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: OS(Phase I: End of 6 months, 12 months, 24 months.)
- Phase I and II: DFS(Through study completion, up to 2 years)
- Phase I and II: Evaluate incidence of AEs and SAEs(Through study completion, up to 2 years)
- Phase I and II: Evaluate BH3 priming assay results(Completion of Cycle 1, estimated 1 month)
- Phase II: OS(Phase II: End of 6 months, 12 months, 24 months)