Correlated Drug Terms (0)

Correlated MeSH Terms (6)

Correlated HPO Terms (4)

Primary Outcomes

Description: A DLT is defined as any of the following events that occur within 28 days starting with the first dose on cycle 1 day 1 (C1D1) and that is considered to be related to investigation product (IP). The severity of AEs will be assessed according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. DLT is defined as follows: 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/μL for more than 28 days off therapy and in the absence of evidence of active leukemia or MDS in the marrow or blood, will be considered as a DLT.

Description: An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. AEs will be graded using NCI-CTCAE guidelines, version 5.0.

Description: An AE is considered "serious" if the event: results in death; is life-threatening (An AE is considered "life-threatening" if its occurrence places the subject at immediate risk of death; it does not include an AE that, had it occurred in a more severe form, might have caused death.); 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 (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE); other medically important events.

Description: Number of participants with potentially clinically significant laboratory values.

Description: Routine 12-lead ECGs will be taken after the subject has been resting in the supine position for at least 5 minutes. Routine 12-lead ECGs will be taken in triplicate.

Description: Number of participants with potentially clinically significant vital sign values.

Description: Number of participants with potentially clinically significant physical exam values.

Description: The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.

Description: CRc rate is defined for AML subjects as the number of participants who achieve the best response of CRc (complete response [CR], complete remission with incomplete platelet recovery [CRp] or complete remission with incomplete hematological recovery [CRi]) divided by the number of participants in the analysis population.

Description: Complete response + bone marrow complete response + partial response (CR + BM CR + PR) rate for participants with R/R higher risk MDS (phase 2) [ Time Frame: Up to 2 years ] CR + BM CR + PR rate is defined for MDS participants as the number of participants who achieve the best response of CR + BM CR + PR divided by the number of subjects in the analysis population.

Secondary Outcomes

Description: Duration of remission for participants with AML includes 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).

Description: Duration of remission for MDS includes duration of CR and duration of response (i.e., CR + PR).

Description: EFS is 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 occurs first earliest of [relapse date, treatment failure date, death date] - first dose date + 1).

Description: OS is defined as the time from the date of first dose until the date of death from any cause (death date - first dose date + 1).

Description: CR rate is defined as the number of participants who achieve CR at any of the postbaseline visits divided by the number of participants in the analysis population.

Description: Best response rate is defined as the number of subjects who achieve CRc or PR at any of the postbaseline visits divided by the number of subjects in the analysis population.

Description: CRh rate is defined as the number of participants who achieve CRh at any of the postbaseline visits divided by the number of participants in the analysis population.

Description: CR rate is defined as the number of participants who achieve CR at any of the postbaseline visits divided by the number of participants in the analysis population.

Description: HI requires 1 measurement of erythroid or platelets or neutrophils maintained at a specified level for at least 8 weeks without ongoing cytotoxic therapy

Description: Objective response (CR + BM CR + PR + HI) rates (ORR) for participants with R/R higher risk MDS [Time Frame: Up to 2 years] ORR is defined as the number of participants who achieve CR or BM CR or PR or HI at any of the postbaseline visits divided by the number of participants in the analysis population.

HP:0006733: Acute megakaryocytic leukemia

Genes 1

Protein Mutations 0

SNP 0

HP:0004808: Acute myeloid leukemia

Genes 48

Protein Mutations 22

SNP 4

HP:0001909: Leukemia

Genes 190

Protein Mutations 56

SNP 17

HP:0002863: Myelodysplasia

Genes 94

Protein Mutations 22

SNP 0

HP:0012324: Myeloid leukemia

Genes 20

Protein Mutations 33

SNP 9