A 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)

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.

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.

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.

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 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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

EOT was calculated as last dose plus 7 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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

EOT was calculated as last dose plus 7 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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

OP was the period observed after the last dose.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

OP was the period observed after the last dose.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

OP was the period observed after the last dose.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

OP was the period observed after the last dose.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

OP was the period observed after the last dose.

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.

• 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.
• Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
• Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
• Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.

OP was the period observed after the last dose.

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.

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.

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.

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.

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%.

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.

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%.

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).

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)

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)