NCT03969420终止2 期
A Phase 2, Open-label, Randomized, Two-stage Clinical Study of Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia Following Treatment With Venetoclax Combination Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 18
- 主要终点
- Combined Complete Remission
研究概览
简要总结
This study will evaluate the safety and efficacy of alvocidib in patients with AML who have either relapsed from or are refractory to venetoclax in combination with azacytidine or decitabine.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Be ≥18 years of age.
- •Have an established, pathologically confirmed diagnosis of AML by World Health Organization (WHO) criteria, excluding acute promyelocytic leukemia (APL-M3) with a bone marrow of >5% blasts based on histology or flow cytometry.
- •Have received initial induction therapy with venetoclax in combination with azacytidine or decitabine (with or without other investigational agents as part of a clinical trial; requires Medical Monitor review) and were either refractory (failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days) or have relapsed (reoccurrence of disease following a CR/CRi with duration ≥90 days).
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤
- •Have a glomerular filtration rate (GFR) ≥30 mL/min using the Cockcroft-Gault equation.
- •Have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≤5 times upper limit of normal (ULN).
- •Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia).
- •Be infertile or agree to use an adequate method of contraception:sexually active patients and their partners must use an effective method of contraception associated with a low failure rate prior to study entry, for the duration of study participation, and for at least 3 months (males) and 6 months (females) after the last dose of study drug.
- •Be able to comply with the requirements of the entire study.
- •Provide written informed consent prior to any study related procedure: in the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new informed consent form must be signed.
排除标准
- •Received any previous treatment with alvocidib or any other CDK inhibitor or received prior anti-leukemic therapy other than first-line venetoclax in combination with azacytidine or decitabine.
- •Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting treatment on either arm.
- •Received an allogeneic stem cell transplant within 60 days of the start of study treatment. Patients who received an allogeneic stem cell transplant must be off all immunosuppressants at the time of study treatment
- •Are receiving or have received systemic therapy for graft-versus-host disease.
- •Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #2 above).
- •Received antileukemic therapy within the last 2 weeks or 3-5 half lives of the prior therapy (with the exception of hydroxyurea or if the patient has definite refractory disease), whichever is less. Refractory patients who received therapy within the last 2 weeks may be eligible with prior approval of the Medical Monitor.
- •Diagnosed with acute promyelocytic leukemia (APL-M3).
- •Have active central nervous system (CNS) leukemia.
- •Have evidence of uncontrolled disseminated intravascular coagulation.
- •Have an active, uncontrolled infection.
- •Have other life-threatening illness.
- •Have other active malignancies requiring treatment or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia.
- •Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.
- •Are pregnant and/or nursing.
- •Have received any live vaccine within 14 days prior to first study drug administration.
研究组 & 干预措施
Lead-In Cohort: Arm 1
Experimental
Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days)
干预措施: Alvocidib (flavopiridol) and cytarabine (Ara-C) (Drug)
Lead-In Cohort: Arm 2
Experimental
Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days).
干预措施: Alvocidib (flavopiridol) (Drug)
Stage 1: Arm 1
Experimental
Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days)
干预措施: Alvocidib (flavopiridol) and cytarabine (Ara-C) (Drug)
Stage 1: Arm 2
Experimental
Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days).
干预措施: Alvocidib (flavopiridol) (Drug)
结局指标
主要结局
Combined Complete Remission
时间窗: Response assessments were measured from date of first dose through End of Treatment date, an average of 3 months.
Rate of combined complete remission (complete remission (CR) + CR with incomplete hematological recovery (CRi)), as defined by the International Working Group Criteria and 2017 European LeukemiaNet). Combined complete remissions (patients with a best response of CR or CRi), complete remissions, composite complete remissions (patients with a best response of CR, CRi or CRh), and combined responses (patients with a best response of CR, CRi, CRh, MLFS or PR) will be summarized by observed response rates and estimated 95% CIs.
次要结局
- Complete Response Rate(Response assessments were measured from date of first dose through end of treatment date, an average of 3 months)
- Composite CR Rate(Response assessments were measured from date of first dose through end of treatment date, an average of 3 months)
- Combined Response Rate(Response assessments were measured from date of first dose through end of treatment date, an average of 3 months)
- Transfusion Independence(Transfusion dependence was measured from 28 days prior to first dose through 56 days after last dose, an average of 6 months)
- Median Overall Survival(From first dose until disease progression or death; through study termination, an average of 10 months)
- Event Free Survival (EFS)(From first dose until disease progression or death; through study termination, an average of 10 months)
- Duration of Composite Complete Remission (CR)(Response assessments were measured from date of first dose through end of treatment date, an average of 3 months)
研究者
研究点 (18)
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