A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 16
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study was to evaluate the safety and tolerability and to determine the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) of ASP7517.
This study also evaluated the clinical response of ASP7517 as well as other measures of anticancer activity of ASP7517.
详细描述
This study consisted of 2 parts: phase 1 dose escalation and phase 2 dose expansion.
Phase 1 Dose Escalation:
Approximately 18 subjects with either relapsed/refractory (R/R) AML or R/R higher risk MDS were enrolled. Participants received 2 single doses of ASP7517 via intravenous infusion. Dosing occured on day 1 of each cycle. Each cycle was defined as 28 days with a total of 2 treatment cycles.
Participants were managed under hospitalization for at least 7 days during the first cycle of the dose escalation phase. In addition, prior to hospital discharge, participant safety was ensured by performing medical tests and procedures listed on day 7 of cycle 1 and tests considered clinically necessary to evaluate the participant's general condition and adverse event (AE) resolution. The participant was also followed on an outpatient basis on planned visits during cycles 1 and 2 after hospital discharge during the dose limiting toxicity (DLT) assessment period to closely monitor any AEs. Participants were hospitalized days 1 to 7 during cycle 2.
Phase 2 Dose Expansion:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Subject diagnosed with R/R AML or R/R higher risk MDS is defined as:
- •R/R AML: Morphologically documented primary or secondary AML by the WHO criteria (2016); and refractory to at least 2 cycles of induction chemotherapy/not a candidate for re-induction or relapsed after achieving remission with a prior therapy; and received all standard therapies including targeted therapies (unless the therapy is contraindicated or intolerable) which are known to provide clinical benefit in the opinion of the treating investigator; and received salvage therapy or is not a candidate for salvage therapy.
- •R/R higher risk MDS: Has MDS by the WHO criteria (2016); and either relapsed after achieving remission or refractory to standard therapies, including ≥ 4 cycles of hypomethylating agents (unless the therapy is contraindicated or intolerable); and is classified as higher risk MDS with a score of > 3.5 by Revised International Prognostic Scoring System (IPSS-R) in MDS.
- •Subject has an Eastern Cooperative Oncology Group performance status of ≤
- •Subject must meet the following criteria as indicated on the clinical laboratory tests during screening period:
- •Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × upper limit of normal (ULN).
- •Serum total bilirubin ≤ 1.5 × ULN.
- •Serum creatinine ≤ 1.5 × ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
- •Platelets ≥ 50,000/μL at cycle 1 day 1 (C1D1) in the dose escalation cohorts only.
- •Subject has a life expectancy of ≥ 12 weeks at the time of screening.
- •Subjects with AML must have peripheral blood absolute blast count of < 20,000/μL at C1D
- •Note: Blast count can be controlled by hydroxyurea during screening period.
- •Female subject is not pregnant and at least 1 of the following conditions apply:
- •Not a woman of childbearing potential (WOCBP).
- •WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 180 days after final study treatment administration.
- •Female subject must agree not to breastfeed starting at screening and throughout the study period and for 180 days after the final study treatment administration.
- •Female subject must not donate ova starting at first dose of investigational product (IP) and throughout the study period and for 180 days after final study treatment administration.
- •Male subject with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 180 day after final study treatment administration.
- •Male subject must not donate sperm during the treatment period and for 180 days after the final study treatment administration.
- •Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 180 days after final study treatment administration.
- •Subject agrees not to participate in another interventional study while receiving study treatment in the present study.
排除标准
- •Subject was diagnosed with acute promyelocytic leukemia.
- •Subject has breakpoint cluster region-Abelson-positive leukemia (BCR-ABL).
- •Subject has persistent non-hematological toxicities of ≥ grade 2 (National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI-CTCAE], version 5.0), with symptoms and objective findings from prior AML or MDS treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation or surgery).
- •Subject has received any of the following therapies:
- •Systemic immunomodulators or immunosuppressive drugs including steroids ≤ 28 days prior to C1D1 (steroids can be used if not intended for treatment of AML or MDS; steroids for AML/MDS related symptoms can be used at low doses [less than 10 mg/day dexamethasone]).
- •Cytotoxic agents (except hydroxyurea given for controlling blast cells) ≤ 28 days prior to C1D
- •Investigational products for the treatment of AML or MDS within 5 half-lives prior to screening visit.
- •Hematopoietic stem cell transplant (HSCT).
- •Radiation therapy ≤ 28 days prior to C1D
- •Subject has clinically active nervous system leukemia.
- •Subject has active or prior documented autoimmune or inflammatory disorders requiring systemic treatment.
- •Subject has ongoing, untreated malignancy with the exception of the following:
- •Subjects with treated non-melanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed.
- •Subjects with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed or treated with definitive radiotherapy.
- •Subject with left ventricular ejection fraction of < 45% on echocardiogram or multigated acquisition scan (MUGA) performed within 28 days of screening.
- •Subject has laboratory abnormalities, or clinical evidence of disseminated intravascular coagulation, or ongoing history of coagulation disorder manifested by bleeding or clotting.
- •Subject has an active uncontrolled infection.
- •Subject is known to have human immunodeficiency virus infection.
- •Subject has active hepatitis B or C or other active hepatic disorder.
- •Subject has any condition which makes the subject unsuitable for study participation.
- •Subject has a known or suspected hypersensitivity to bovine-derived protein or has suspected hypersensitivity to any ingredients of ASP
- •Subject is eligible for HSCT.
研究组 & 干预措施
Dose Escalation (Phase 1): ASP7517 1x10^6 cells/mL
Participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) and R/R higher risk Myelodysplastic Syndrome (MDS) received intravenous (IV) infusion of ASP7517 (human embryonic kidney cell [HEK293] transfected with encoding target WT-1) at a dose of 1x10^6 cells/milliliters (mL) at 4 to 6 mL/minute infusion rate on day 1 of each cycle for 2 doses (1 cycle= 28 days).
干预措施: ASP7517 (Biological)
Dose Escalation (Phase 1): ASP7517 1x10^7 cells/mL
Participants with R/R AML and R/R higher risk MDS received IV infusion of ASP7517 (HEK293 transfected with encoding target WT-1) at a dose of 1x10^7 cells/mL at 4 to 6 mL/minute infusion rate on day 1 of each cycle for 2 doses (1 cycle= 28 days).
干预措施: ASP7517 (Biological)
Dose Escalation (Phase 1): ASP7517 1x10^8 cells/mL
Participants with R/R AML and R/R higher risk MDS received IV infusion of ASP7517 (HEK293 transfected with encoding target WT-1) at a dose of 1x10^8 cells/mL at 4 to 6 mL/minute infusion rate on day 1 of each cycle for 2 doses (1 cycle= 28 days).
干预措施: ASP7517 (Biological)
Dose Expansion (Phase 2: AML): ASP7517 1x10^8 cells/mL
Participants with R/R AML received IV infusion of ASP7517 (HEK293 transfected with encoding target WT-1) at a dose of 1x10^8 cells/mL at 4 to 6 mL/minute infusion rate on day 1 of each cycle for 6 doses (1 cycle= 28 days).
干预措施: ASP7517 (Biological)
Dose Expansion (Phase 2: MDS): ASP7517 1x10^8 cells/mL
Participants with R/R higher risk MDS received IV infusion of ASP7517 (HEK293 transfected with encoding target WT-1) at a dose of 1x10^8 cells/mL at 4 to 6 mL/minute infusion rate on day 1 of each cycle for 6 doses (1 cycle= 28 days).
干预措施: ASP7517 (Biological)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Day 1 up to 28 days
DLT was defined as any of the following events that occurred within 28 days starting with the first dose on cycle 1 day 1 (C1D1) and that was considered to be related to study drug. DLT was defined as follows: * Grade 3 of more : non-hematologic AEs that are ≥ grade 3 * Confirmed Hy's law case * New onset of grade 4 thrombocytopenia (with minimum of 2 grade worsening from baseline) within 24 hours of dosing * Prolonged myelosuppression, defined as absolute neutrophil count (ANC) \< 500/microliter (μL) for more than 28 days off therapy and in the absence of evidence of active leukemia or MDS in the marrow or blood.
Phase 2: Complete Remission + Bone Marrow Complete Remission + Partial Remission (CR + BM CR + PR) Rate for Participants With R/R Higher Risk MDS
时间窗: From first dose up to 43 months
Percentage of participants with CR+BM CR+ PR was reported. CR, BM CR and PR achieved for minimum of 4 weeks; CR: bone marrow: ≤ 5% myeloblasts with normal maturation of all cell Lines, peripheral blood evaluation (hemoglobin (Hb) ≥ 11 g/dL, platelets ≥ 100 × 10\^9/L, neutrophils ≥ 1.0 × 10\^9/L, 0% blasts in blood) BM CR: bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment PR: achieved all CR criteria except bone marrow blasts decreased by ≥ 50% over pretreatment but still \> 5%, cellularity and morphology not relevant.
Number of Participants With ECOG Performance Status at Cycle 1(C1) Day2(D2)
时间窗: C1D2
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C1D11
时间窗: C1D11
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C1D25
时间窗: C1D25
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With Treatment Emergent Adverse Events (TEAE) & Serious TEAE
时间窗: From first dose up to 43 months
An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An AE was considered "serious" if, it resulted in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly, or birth defect; requires inpatient hospitalization; or leads to prolongation of hospitalization; other medically important events. TEAE was defined as an AE observed after starting administration of the study drug. TEAEs included both Serious and non-serious AEs.
Number of Participants With ECOG Performance Status at C1D18
时间窗: C1D18
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C2D8
时间窗: C2D8
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C6D15
时间窗: C6D15
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Phase 2: Composite Complete Remission (CRc) Rate for Participants With R/R AML
时间窗: From first dose up to 43 months
Percentage of participants with CRc was reported. CRc:defined as rate of all complete \& incomplete remissions (CR + CR with incomplete platelet recovery \[CRp\] + CR with incomplete hematological recover \[Cri\]). CR: achieved morphologic leukemia-free state \& their bone marrow was regenerating normal hematopoietic cells. If absolute neutrophil count (ANC) ≥ 1×10\^9/L, platelet count (PC) ≥ 100×10\^9/L, normal marrow differential \< 5% blasts, \& were red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion \& platelet transfusion prior to disease assessment). There was no evidence of extramedullary leukemia or Auer rods \& blast counts in peripheral blood must be ≤ 2%. CRp: must achieve CR except for incomplete platelet recovery (\< 100×10\^9/L). CRi: must fulfil CR except for incomplete hematological recovery with residual neutropenia (ANC \< 1×10\^9/L), with or without complete platelet recovery. RBC and platelet transfusion independence not required.
Number of Participants With ECOG Performance Status at C2D2
时间窗: C2D2
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C2D4
时间窗: C2D4
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C3D1
时间窗: C3D1
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C3D15
时间窗: C3D15
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C5D1
时间窗: C5D1
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C1D4
时间窗: C1D4
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C1D8
时间窗: C1D8
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C1D15
时间窗: C1D15
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C1D22
时间窗: C1D22
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C2D1
时间窗: C2D1
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C2D15
时间窗: C2D15
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C2D22
时间窗: C2D22
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C4D1
时间窗: C4D1
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C4D15
时间窗: C4D15
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C5D15
时间窗: C5D15
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at C6D1
时间窗: C6D1
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead.
Number of Participants With ECOG Performance Status at OP (Week 6)
时间窗: OP (week 6)
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead. OP was the period observed after the last dose.
Number of Participants With ECOG Performance Status at End of Treatment (EOT) (Dose Escalation Phase)
时间窗: EOT (up to 63 Days)
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead. EOT was calculated as last dose plus 7 days.
Number of Participants With ECOG Performance Status at OP (Week 8)
时间窗: OP (week 8)
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead. OP was the period observed after the last dose.
Number of Participants With ECOG Performance Status at EOT (Dose Expansion Phase)
时间窗: EOT (up to 175 days)
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead. EOT was calculated as last dose plus 7 days.
Number of Participants With ECOG Performance Status at Observation Period (OP) (Week 2)
时间窗: OP (week 2)
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead. OP was the period observed after the last dose.
Number of Participants With ECOG Performance Status at OP (Week 4)
时间窗: OP (week 4)
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead. OP was the period observed after the last dose.
Number of Participants With ECOG Performance Status at OP (Week 10)
时间窗: OP (week 10)
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead. OP was the period observed after the last dose.
Number of Participants With ECOG Performance Status at OP (Week 12)
时间窗: OP (week 12)
Number of participants with ECOG PS was reported. ECOG performance status was measured on a 6 point grade scale. 0: Fully active, able to carry on all pre-disease performance without restriction. 1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead. OP was the period observed after the last dose.
次要结局
- Duration of Remission (DR) for Participants With R/R Higher Risk MDS(From first response up to 43 months)
- Event Free Survival (EFS)(From first dose up to 43 months)
- Objective Response (OR) (CR + BM CR + PR + HI) Rates (ORR) for Participants With R/R Higher Risk MDS(From first dose up to 43 months)
- Duration of Remission (DR) for Participants With R/R AML(From first response up to 43 months)
- CRh for Participants With R/R AML(From first dose up to 43 months)
- CR for Participants With R/R Higher Risk MDS(From first dose up to 43 months)
- Overall Survival (OS)(From first dose up to 43 months)
- CR for Participants With R/R AML(From first dose up to 43 months)
- Best Response (CRc + PR) Rates for Participants With R/R AML(From first dose up to 43 months)
- Hematologic Improvement (HI) for Participants With R/R Higher Risk MDS(From first dose up to 43 months)