A Study of BH-30236 in Relapsed/ Refractory Acute Myelogenous Leukemia and Higher Risk Myelodysplastic Syndrome
NCT Number: NCT06501196
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Leukemia|Leukemia, Myeloid|Leukemia, Myeloid, Acute|Preleukemia|Myelodysplastic Syndromes|Refractory Acute Myeloid Leukemia
Interventions: DRUG: BH-30236
Sponsor: BlossomHill Therapeutics
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 74
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-06-19
Completion Date: 2027-06
Locations: Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States|Sarah Cannon Research Institute, Nashville, Tennessee, 37203, United States

Summary:
Study BH-30236-01 is a first-in-human (FIH), Phase 1/1b, open-label, dose escalation and expansion study in participants with relapsed/refractory acute myelogenous leukemia (R/R AML) or higher-risk myelodysplastic syndrome (HR-MDS).

Phase 1 (Dose Escalation) will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of BH-30236 administered orally. Approximately 50 participants may be enrolled in Phase 1 of the study.

Phase 1b (Dose Expansion) will follow Phase 1 to further understand the relationships among dose, exposure, toxicity, tolerability, and clinical activity. Up to 24 participants may be enrolled in Phase 1b of the study.

The dose expansion part (Phase 1b) will be followed to understand the relationships among dose, exposure, toxicity, tolerability and clinical activity. Up to 24 participants may be enrolled in Phase 1b of the study.

Primary Outcome Measures: Dose Escalation: Frequency of dose limiting toxicities (DLTs), DLTs are dose-limiting toxicities as defined in the study protocol., Dose-limiting toxicities are collected during the first treatment cycle (28 days)|Dose Escalation and Expansion: Safety evaluation of BH-30236: Number of participants with treatment-related adverse events as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, Frequency, severity and relationship to study drug of AEs and SAEs, From first dose until 28 days after last dose of BH-30236|Dose Expansion: Composite Complete Remission (CR) Rate, Composite CR rate disease assessment in accordance with the following guidelines: European Leukemia Network (ELN) 2022 for acute myelogenous leukemia (AML) and International Working Group (IWG) 2023 for myelodysplastic syndrome (MDS)., From first dose of BH-30236 until disease progression (up to approximately 1 year)
Secondary Outcome Measures: Dose Escalation and Expansion: Maximum observed blood concentration (Cmax) of BH-30236., Blood samples for PK analyses will be collected at predetermined time points and analyzed., Evaluation performed in Cycle 1 (cycle duration is 28 days).|Dose Escalation: Area under the blood concentration time curve (AUC) of BH-30236., Blood samples for PK analyses will be collected at predetermined time points and analyzed., Evaluation performed in Cycle 1 (cycle duration is 28 days).|Dose Escalation and Expansion: Concentration before dose at steady state (Ctrough)., Blood samples for PK analyses will be collected at predetermined time points and analyzed., Evaluation performed in all treatment cycles up to one year (cycle duration is 28 days).|Dose Escalation and Expansion: Objective Response Rate (ORR), Objective response rate disease assessments in accordance with the following guidelines: ELN 2022 recommendations for AML and IWG 2023 for MDS (CR, CR with partial hematologic recovery \[CRh\], CR with incomplete count recovery \[CRi\], CR with limited count recovery \[CRL\], morphologic leukemia-free state \[MLFS\], or partial response \[PR\])., From first dose of BH-30236 until disease progression (up to approximately 1 year)|Dose Escalation and Expansion: Duration of Response (DoR), Time from first documented response until the date of relapse or death., Time from first documented response until disease progression or death (approximately 1 year).|Dose Escalation and Expansion: Time to remission (TTR), Time from first dose to the achievement of first remission Disease assessments will follow the following guidelines: ELN 2022 for AML and IWG 2023 for MDS., From first dose of BH-30236 until complete remission, disease progression or death (approximately 1 year).|Dose Escalation and Expansion: Relapse-free Survival (RFS), The time from the start of treatment date to disease progression, death, or initiation of a new anti-leukemic therapy., From first dose of BH-30236 until disease progression, death, or initiation of a new anti-leukemic therapy (approximately 1 year).|Dose Escalation and Expansion: Measurable Residual Disease (MRD), For AML, using ELN 2022 criteria for disease assessment from Screening, then at the beginning of Cycle 2 and 3, and then every second cycle thereafter., From time of first dose until discontinuation of BH-30236 (approximately 1 year).|Dose Escalation and Expansion: Measurement of the change in RNA alternative splicing markers on BH-30236 treatment, Peripheral blood samples for pharmacodynamic (PD) analyses will be collected at predetermined time points and analyzed., From time of first dose until discontinuation of BH-30236 (approximately 1 year).|Dose Escalation and Expansion: Complete remission (CR) / complete remission with partial hematologic recovery (CRh) rate for AML and complete remission/partial remission (CR/PR) rate for HR-MDS, In accordance with the following guidelines: ELN 2022 recommendations for AML and IWG 2023 for MDS (CR, CR with partial hematologic recovery \[CRh\], CR with incomplete count recovery \[CRi\], CR with limited count recovery CRL, morphologic leukemia-free state \[MLFS\], or partial response \[PR\]), Time from first documented response until disease progression or death (approximately 1 year)