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)

NCT04079296 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 7517-CL-0101
• Study Type: interventional
• Target: 43
• Locations: 2 countries
• Sites: 16

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.

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome

Keywords

ASP7517; Safety; Efficacy; Tolerability

Outcome Measures

Primary Outcomes (34)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  OP (week 12)

Secondary Outcomes (10)

• Duration of Remission (DR) for Participants With R/R AML

  From first response up to 43 months

• 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

• Overall Survival (OS)

  From first dose up to 43 months

• CR for Participants With R/R AML

  From first dose up to 43 months

Study Arms (5)

Dose Escalation (Phase 1): ASP7517 1x10^6 cells/mL

EXPERIMENTAL

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).

Biological: ASP7517

Dose Escalation (Phase 1): ASP7517 1x10^7 cells/mL

EXPERIMENTAL

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).

Biological: ASP7517

Dose Escalation (Phase 1): ASP7517 1x10^8 cells/mL

EXPERIMENTAL

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).

Biological: ASP7517

Dose Expansion (Phase 2: AML): ASP7517 1x10^8 cells/mL

EXPERIMENTAL

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).

Biological: ASP7517

Dose Expansion (Phase 2: MDS): ASP7517 1x10^8 cells/mL

EXPERIMENTAL

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).

Biological: ASP7517

Interventions

ASP7517 BIOLOGICAL

Intravenous (IV)

Dose Escalation (Phase 1): ASP7517 1x10^6 cells/mL; Dose Escalation (Phase 1): ASP7517 1x10^7 cells/mL; Dose Escalation (Phase 1): ASP7517 1x10^8 cells/mL; Dose Expansion (Phase 2: AML): ASP7517 1x10^8 cells/mL; Dose Expansion (Phase 2: MDS): ASP7517 1x10^8 cells/mL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≤ 2.
• Subject must meet the following criteria as indicated on the clinical laboratory tests during screening period:
• Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × upper limit of normal (ULN).
• Serum total bilirubin ≤ 1.5 × ULN.
• Serum creatinine ≤ 1.5 × ULN or an estimated glomerular filtration rate of \> 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
• Platelets ≥ 50,000/μL at cycle 1 day 1 (C1D1) in the dose escalation cohorts only.
• Subject has a life expectancy of ≥ 12 weeks at the time of screening.
• Subjects with AML must have peripheral blood absolute blast count of \< 20,000/μL at C1D1. Note: Blast count can be controlled by hydroxyurea during screening period.
• Female subject is not pregnant and at least 1 of the following conditions apply:
• Not a woman of childbearing potential (WOCBP).
• WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 180 days after final study treatment administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period and for 180 days after the final study treatment administration.

You may not qualify if:

• 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 C1D1.
• 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 C1D1.
• Subject has clinically active nervous system leukemia.
• Subject has active or prior documented autoimmune or inflammatory disorders requiring systemic treatment.
• Subject has ongoing, untreated malignancy with the exception of the following:
• Subjects with treated non-melanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed.
• Subjects with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed or treated with definitive radiotherapy.
• Subject with left ventricular ejection fraction of \< 45% on echocardiogram or multigated acquisition scan (MUGA) performed within 28 days of screening.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (16)

City of Hope

Duarte, California, 91010, United States

Location

Memorial Healthcare System-West

Pembroke Pines, Florida, 33028, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Site JP81005

Nagoya, Aichi-ken, Japan

Location

Site JP81016

Matsuyama, Ehime, Japan

Location

Site JP81009

Yoshida-gun, Fukui, Japan

Location

Site JP81004

Maebashi, Gunma, Japan

Location

Site JP81007

Kobe, Hyōgo, Japan

Location

Site JP81013

Isehara, Kanagawa, Japan

Location

Site JP81017

Sendai, Miyagi, Japan

Location

Site JP81001

Shinagawa, Tokyo, Japan

Location

Site JP81002

Fukuoka, Japan

Location

Site JP81010

Gifu, Japan

Location

Site JP81008

Okayama, Japan

Location

Site JP81011

Osaka, Japan

Location

Site JP81012

Osaka, Japan

Location

Related Links

• Link to plain language summary of the study on the Trial Results Summaries website.
• Link to results and other applicable study documents on the Astellas Clinical Trials website.

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development Inc

astellas.resultsdisclosure@astellas.com

8008887704

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: September 6, 2019
• Study Start: September 19, 2019
• Primary Completion: April 21, 2023
• Study Completion: April 21, 2023
• Last Updated: November 26, 2024
• Results First Posted: June 25, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); JP (13)