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)
Overview
- Phase
- Phase 1
- Intervention
- ASP7517
- Conditions
- Acute Myeloid Leukemia (AML)
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 43
- Locations
- 16
- Primary Endpoint
- Number of Participants With Dose Limiting Toxicities (DLTs)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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: Approximately 104 participants per dose level were enrolled. Each dose level enrolled up to 52 R/R AML participants and up to 52 R/R higher risk MDS participants. Both groups of participants were enrolled in parallel and independently. The number of dose levels investigated during phase 2 were based upon the data from phase 1. When escalation and expansion cohorts were both open for enrollment, enrollment into escalation cohorts took priority such that participants who were eligible for both were preferentially enrolled in the escalation cohorts.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
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).
Intervention: ASP7517
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).
Intervention: ASP7517
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).
Intervention: ASP7517
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).
Intervention: ASP7517
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).
Intervention: ASP7517
Outcomes
Primary Outcomes
Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: 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
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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.
Secondary Outcomes
- 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)