A Two-Part Phase 1b Study Evaluating the Combination of Tazemetostat and CPX-351 (Part 1) and Palbociclib Pre-Treatment Followed by CPX-351 (Part 2) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Incidence of grade >= 3 non-hematologic dose limiting toxicities
研究概览
简要总结
This is a two-part phase Ib dose escalation study to evaluate the safety and preliminary efficacy of the combination of tazemetostat and CPX-351 (Part 1) and of pre-treatment with palbociclib followed by CPX-351 (Part 2) for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). Part 1 of the study will seek to establish the safety, tolerability, biological activity and recommended dose for further evaluation (RDFE) of tazemetostat in combination with standard-dose CPX-351. Part 2 of the study will seek to establish the safety, tolerability, biological activity RDFE of pre-treatment palbociclib prior CPX-351.
详细描述
PRIMARY OBJECTIVE:
Part 1: To determine the RDFE of tazemetostat in combination with CPX-351 in patients with R/R-AML.
Part 2: To determine the RDFE of palbociclib pre-treatment prior to CPX-351 in patients with R/R-AML.
SECONDARY OBJECTIVE:
I. To evaluate the preliminary efficacy of tazemetostat in combination with CPX-351 (Part 1) and of palbociclib pre-treatment followed by CPX-351 (Part 2).
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
- •Provide signed and dated informed consent form
- •Willing to comply with all study procedures and be available for the duration of the study
- •Male or female >= 18 years of age
- •Histologically confirmed acute myeloid leukemia (non-M3) relapsed from or refractory to at least 1 prior line of therapy. Bone marrow aspirate and biopsy within 28 days of screening is acceptable. If no prior bone marrow biopsy is available, bone marrow biopsy must be performed during screening unless:
- •* If the subject has >= 20% myeloblasts present in the peripheral blood, a bone marrow biopsy is not necessary to meet this criterion
- •Treatment with a prior investigational agent is acceptable so long as it has not been administered within 2 weeks of enrollment and any prior adverse effects have resolved to grade 1 or less with the exception of alopecia
- •Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
- •Life expectancy of at least 4 weeks
- •Must be able to consume oral medication
- •Subjects must have recovered from the toxic effect of any prior therapy to =< grade 1 (except alopecia)
- •Creatine clearance (CrCL) >= 45
- •Total bilirubin < 2 x upper limit of normal (ULN)
- •Female subjects of childbearing age must have a negative pregnancy test
排除标准
- •Subjects with acute promyelocytic leukemia
- •Subjects receiving any active chemotherapy agents (except hydroxyurea). Intrathecal methotrexate and cytarabine are permissible
- •Subjects whose participation would result in a total cumulative dose of daunorubicin greater than 550 mg/m^2 or greater than 450 mg/m^2 if they previously received mediastinal radiation
- •Subjects with evidence of active central nervous system (CNS) leukemia involvement. Lumbar puncture is not required for enrollment in the absence of neurologic symptoms
- •Subjects must not be receiving growth factors (except erythropoietin)
- •Subjects with currently active second malignancy with the exception of nonmelanoma skin cancer, carcinoma in situ of the cervix, resected prostate cancer with Gleason score =< 6
- •Subjects with unstable cardiac disease or uncontrolled arrhythmia
- •Subjects with other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate to receive high-intensity therapy
- •Subjects who are pregnant or breastfeeding
- •Subjects with known allergic reactions to components of the study product(s)
- •Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study
研究组 & 干预措施
Part I (tazemetostat, CPX-351)
Patients receive tazemetostat PO BID on days -1 to 6, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
干预措施: Tazemetostat (Drug)
Part I (tazemetostat, CPX-351)
Patients receive tazemetostat PO BID on days -1 to 6, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Part I (tazemetostat, CPX-351)
Patients receive tazemetostat PO BID on days -1 to 6, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
干预措施: Bone Marrow Aspiration and Biopsy (Procedure)
Part I (tazemetostat, CPX-351)
Patients receive tazemetostat PO BID on days -1 to 6, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
干预措施: Biospecimen Collection (Procedure)
Part II: (Palbociclib Pre-Treatment Followed by CPX-351)
Patients receive palbociclib PO QD on days -3 to -1 and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
干预措施: Bone Marrow Aspiration and Biopsy (Procedure)
Part II: (Palbociclib Pre-Treatment Followed by CPX-351)
Patients receive palbociclib PO QD on days -3 to -1 and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
干预措施: Tazemetostat (Drug)
Part II: (Palbociclib Pre-Treatment Followed by CPX-351)
Patients receive palbociclib PO QD on days -3 to -1 and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Part II: (Palbociclib Pre-Treatment Followed by CPX-351)
Patients receive palbociclib PO QD on days -3 to -1 and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
干预措施: Biospecimen Collection (Procedure)
Part II: (Palbociclib Pre-Treatment Followed by CPX-351)
Patients receive palbociclib PO QD on days -3 to -1 and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
干预措施: Palbociclib (Drug)
结局指标
主要结局
Incidence of grade >= 3 non-hematologic dose limiting toxicities
时间窗: Up to 1 year
The primary outcome measure will be grade \>= 3 non-hematologic dose limiting toxicities. Adverse events will be coded by organ system and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0. the calculation of adverse events incidences will be passed on number of patients per adverse event category. Standard proportions will be used to report rates of safety endpoints. Summary tables will be presented by dose level, seriousness, severity and relatedness.
次要结局
- Partial remission (PR)(Up to 1 year)
- Relapse free survival(The time measured in months to relapse from day 1 of treatment, assessed up to 1 year)
- Complete response(Up to 1 year)
- Relapse(Up to 1 year)
- Overall survival(The time measured in months from day 1 of treatment, assessed up to 1 year)
- Time to transplant(The time measured in months to allogeneic stem cell transplantation from day 1 of treatment, assessed up to 1 year)
- Incidence of adverse events(Up to 1 year)
- Induction failure/refractory acute myeloid leukemia (AML)(Up to 1 year)
- Time to blood count recovery(The number of days until ANC > 1.0 x 10^9/L and platelets >= 100 x 10^9/L from day 1 of treatment, assessed up to 1 year)
- Rate of allogeneic stem cell transplantation(Up to 1 year)