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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
43
Intravenous (IV)
City of Hope
Duarte, California, United States
Memorial Healthcare System-West
Pembroke Pines, Florida, United States
NYU Langone Health
New York, New York, United States
Site JP81005
Nagoya, Aichi-ken, Japan
Site JP81016
Matsuyama, Ehime, Japan
Site JP81009
Yoshida-gun, Fukui, Japan
Site JP81004
Maebashi, Gunma, Japan
Site JP81007
Kobe, Hyōgo, Japan
Site JP81013
Isehara, Kanagawa, Japan
Site JP81017
Sendai, Miyagi, Japan
...and 6 more locations
Number of Participants With Dose Limiting Toxicities (DLTs)
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.
Time frame: Day 1 up to 28 days
Number of Participants With Treatment Emergent Adverse Events (TEAE) & Serious TEAE
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.
Time frame: From first dose up to 43 months
Phase 2: Composite Complete Remission (CRc) Rate for Participants With R/R AML
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.
Time frame: From first dose up to 43 months
Phase 2: Complete Remission + Bone Marrow Complete Remission + Partial Remission (CR + BM CR + PR) Rate for Participants With R/R Higher Risk MDS
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.
Time frame: From first dose up to 43 months
Number of Participants With ECOG Performance Status at Cycle 1(C1) Day2(D2)
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.
Time frame: C1D2
Number of Participants With ECOG Performance Status at 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.
Time frame: C1D4
Number of Participants With ECOG Performance Status at 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.
Time frame: C1D8
Number of Participants With ECOG Performance Status at 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.
Time frame: C1D11
Number of Participants With ECOG Performance Status at 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.
Time frame: C1D15
Number of Participants With ECOG Performance Status at 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.
Time frame: C1D18
Number of Participants With ECOG Performance Status at 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.
Time frame: C1D22
Number of Participants With ECOG Performance Status at 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.
Time frame: C1D25
Number of Participants With ECOG Performance Status at 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.
Time frame: C2D1
Number of Participants With ECOG Performance Status at 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.
Time frame: C2D2
Number of Participants With ECOG Performance Status at 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.
Time frame: C2D4
Number of Participants With ECOG Performance Status at 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.
Time frame: C2D8
Number of Participants With ECOG Performance Status at 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.
Time frame: C2D15
Number of Participants With ECOG Performance Status at 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.
Time frame: C2D22
Number of Participants With ECOG Performance Status at 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.
Time frame: C3D1
Number of Participants With ECOG Performance Status at 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.
Time frame: C3D15
Number of Participants With ECOG Performance Status at 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.
Time frame: C4D1
Number of Participants With ECOG Performance Status at 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.
Time frame: C4D15
Number of Participants With ECOG Performance Status at 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.
Time frame: C5D1
Number of Participants With ECOG Performance Status at 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.
Time frame: C5D15
Number of Participants With ECOG Performance Status at 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.
Time frame: C6D1
Number of Participants With ECOG Performance Status at 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.
Time frame: C6D15
Number of Participants With ECOG Performance Status at End of Treatment (EOT) (Dose Escalation Phase)
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.
Time frame: EOT (up to 63 Days)
Number of Participants With ECOG Performance Status at EOT (Dose Expansion Phase)
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.
Time frame: EOT (up to 175 days)
Number of Participants With ECOG Performance Status at Observation Period (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.
Time frame: OP (week 2)
Number of Participants With ECOG Performance Status at 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.
Time frame: OP (week 4)
Number of Participants With ECOG Performance Status at 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.
Time frame: OP (week 6)
Number of Participants With ECOG Performance Status at 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.
Time frame: OP (week 8)
Number of Participants With ECOG Performance Status at 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.
Time frame: OP (week 10)
Number of Participants With ECOG Performance Status at 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.
Time frame: OP (week 12)
Duration of Remission (DR) for Participants With R/R AML
DR for AML: included duration of CRc, duration of CR/complete remission with partial hematologic recovery (CRh), duration of CRh, duration of CR, and duration of response (i.e., CRc + PR). CRh: achieved marrow blasts \< 5%, partial hematologic recovery ANC ≥ 0.5 × 10\^9/L and platelets ≥ 50 × 10\^9/L, no evidence of extramedullary leukemia and cannot be classified as CR. The blast counts in peripheral blood was ≤ 2%. PR for AML; achieved bone marrow regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts with decrease of at least 50% in the percentage of blasts in bone marrow aspirate with total marrow blasts between 5% and 25%. Value ≤ 5% blasts was considered PR if Auer rods were present. No evidence of extramedullary leukemia. CR, CRc were defined in outcome measure #3. Kaplan Meier (KM) Estimate was used.
Time frame: From first response up to 43 months
Duration of Remission (DR) for Participants With R/R Higher Risk MDS
DR for MDS: included duration of CR and duration of response (i.e., CR + BM CR + PR). 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. KM Estimate was used.
Time frame: From first response up to 43 months
Event Free Survival (EFS)
EFS was defined as the time from the date of first dose until the date of documented relapse, treatment failure or death from any cause within 30 days after the last dose of study drug (whichever occurred first earliest of \[relapse date, treatment failure date, death date\] - first dose date + 1). Relapse was defined as a reappearance of leukemic blasts in the peripheral blood (\> 2%) or ≥ 5% blasts in the bone marrow aspirate not attributable to any other cause or reappearance or new appearance of extramedullary leukemia or reappearance of significant numbers of peripheral blasts and an increase in the percentage of blasts in the bone marrow aspirate to \> 25% not attributable to any other cause or reappearance or new appearance of extramedullary leukemia. KM Estimate was used.
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Time frame: From first dose up to 43 months
Overall Survival (OS)
OS was defined as the time from the date of first dose until the date of death from any cause (death date - first dose date + 1). For a Participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact (date of last contact - first dose date + 1). KM Estimate was used.
Time frame: From first dose up to 43 months
CR for Participants With R/R AML
Percentage of participants with CR was reported. 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 and blast counts in peripheral blood must be ≤ 2%.
Time frame: From first dose up to 43 months
Best Response (CRc + PR) Rates for Participants With R/R AML
Percentage of participants with best response (CRc + PR) was reported. CRc was defined as rate of all complete and incomplete remissions (CR + CR with incomplete platelet recovery \[CRp\] + CR with incomplete hematological recover \[Cri\]). CR, CRp and CRi were defined in Outcome measure # 3. PR: achieved bone marrow regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts with decrease of at least 50% in the percentage of blasts in bone marrow aspirate with total marrow blasts between 5% and 25%. Value ≤ 5% blasts was considered PR if Auer rods were present. No evidence of extramedullary leukemia.
Time frame: From first dose up to 43 months
CRh for Participants With R/R AML
Percentage of participants with CRh was reported. CRh: achieved marrow blasts \< 5%, partial hematologic recovery ANC ≥ 0.5 × 10\^9/L and platelets ≥ 50 × 10\^9/L, no evidence of extramedullary leukemia and cannot be classified as CR. The blast counts in peripheral blood was ≤ 2%.
Time frame: From first dose up to 43 months
CR for Participants With R/R Higher Risk MDS
Percentage of participants with CR was reported. 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).
Time frame: From first dose up to 43 months
Hematologic Improvement (HI) for Participants With R/R Higher Risk MDS
Percentage of participants with HI was reported. HI: One measurement of the following for at least 8 weeks without cytotoxic therapy: * HI-erythroid: Hb increase of ≥ 1.5 g/dL or RBC transfusions performed for Hb ≤ 9.0 g/dL) * HI-platelets (pre-treatment PC: \>20 ×10\^9/L platelet, absolute increase of ≥ 30 ×10\^9/L and \< 20 ×10\^9/L, platelet absolute increase of \> 20 ×10\^9/L and ≥ 100% increase from pre-treatment level * HI-neutrophils (increase of ≥ 100% from pre-treatment level and an absolute increase of \> 0.5 ×10\^9/L)
Time frame: 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
Percentage of participants with OR (CR + BM CR + PR + HI) was reported. CR, BM CR \& PR achieved for minimum of 4 weeks. CR: BM: ≤ 5% myeloblasts with normal maturation of all cell Lines peripheral blood evaluation (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 \& decrease by ≥ 50% over pretreatment. PR: achieved all CR criteria except bone marrow blasts decreased ≥ 50% over pretreatment but still \> 5% cellularity and morphology not relevant. HI: One measurement of following for at least 8 weeks without cytotoxic therapy. * HI-erythroid: Hb increase of ≥ 1.5 g/dL or RBC transfusions performed for Hb ≤ 9.0 g/dL) * HI-platelets (pre-treatment PC: \>20 ×10\^9/L platelet, absolute increase of ≥ 30 ×10\^9/L and \< 20 ×10\^9/L, platelet absolute increase of \> 20 ×10\^9/L and ≥ 100% increase from pre-treatment level * HI-neutrophils (increase of ≥ 100% from pre-treatment level and an absolute increase of \> 0.5 ×10\^9/L)
Time frame: From first dose up to 43 months