A Study of BH-30236 in Relapsed/ Refractory Acute Myelogenous Leukemia and Higher Risk Myelodysplastic Syndrome
- Conditions
- LeukemiaLeukemia, MyeloidLeukemia, Myeloid, AcuteRefractory Acute Myeloid LeukemiaPreleukemiaMyelodysplastic Syndromes
- Interventions
- Registration Number
- NCT06501196
- Lead Sponsor
- BlossomHill Therapeutics
- Brief 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.
- Detailed Description
This is a Phase 1/1b, multi-center, open-label, dose escalation, first-in-human study to evaluate the safety, tolerability, PK, PD, and preliminary anti-leukemic activity of the CLK inhibitor, BH-30236, in adult subjects with R/R AML or HR-MDS.
The study consists of two parts: Phase 1 Dose Escalation and Phase 1b Dose Expansion.
Phase 1 Dose Escalation is anticipated to enroll approximately 50 subjects to evaluate the safety, tolerability, PK, PD, and preliminary anti-leukemic activity of BH-30236, as well as determine the MTD and/or the preliminary recommended dose(s) for expansion (RDEs).
Phase 1 will follow an accelerated 3 + 3 dose escalation, where participants will receive ascending doses of BH-30236 to determine the recommended RDEs.
Phase 1b Dose Expansion will enroll approximately 24 subjects to evaluate the safety, tolerability, and preliminary anti-leukemic activity of BH-30236 at selected RDEs determined in Phase 1 Dose Escalation.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 74
Not provided
- Diagnosis of acute promyelocytic leukemia or chronic myeloid leukemia with blast crisis.
- Prior allogeneic HSCT within 3 months or donor lymphocyte infusion within 30 days of start of therapy;
- Active and uncontrolled infections.
- Unresolved AEs greater than Grade from prior therapies.
- History of other active malignancy (with certain exceptions)
- Prior treatment with a CLK inhibitor.
- Any acute or chronic graft versus host disease requiring systemic therapy within 4 weeks prior to study drug administration with the exception of topical steroids or the equivalent of 20 mg of prednisone or less.
The above is a summary, other exclusion criteria details may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation Cohort BH-30236 BH-30236 monotherapy for Dose Escalation Dose Expansion Cohort BH-30236 BH-30236 administered at a dose(s) determined form the data of dose escalation cohort
- Primary Outcome Measures
Name Time Method Dose Expansion: Composite Complete Remission (CR) Rate From first dose of BH-30236 until disease progression (up to approximately 1 year) 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).
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 From first dose until 28 days after last dose of BH-30236 Frequency, severity and relationship to study drug of AEs and SAEs
Dose Escalation: Frequency of dose limiting toxicities (DLTs) Dose-limiting toxicities are collected during the first treatment cycle (28 days) DLTs are dose-limiting toxicities as defined in the study protocol.
- Secondary Outcome Measures
Name Time Method Dose Escalation: Area under the blood concentration time curve (AUC) of BH-30236. Evaluation performed in Cycle 1 (cycle duration is 28 days). Blood samples for PK analyses will be collected at predetermined time points and analyzed.
Dose Escalation and Expansion: Relapse-free Survival (RFS) From first dose of BH-30236 until disease progression, death, or initiation of a new anti-leukemic therapy (approximately 1 year). The time from the start of treatment date to disease progression, death, or initiation of a new anti-leukemic therapy.
Dose Escalation and Expansion: Measurable Residual Disease (MRD) From time of first dose until discontinuation of BH-30236 (approximately 1 year). 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.
Dose Escalation and Expansion: Measurement of the change in RNA alternative splicing markers on BH-30236 treatment From time of first dose until discontinuation of BH-30236 (approximately 1 year). Peripheral blood samples for pharmacodynamic (PD) analyses will be collected at predetermined time points and analyzed.
Dose Escalation and Expansion: Time to remission (TTR) From first dose of BH-30236 until complete remission, disease progression or death (approximately 1 year). 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.
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 Time from first documented response until disease progression or death (approximately 1 year) 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 \[PR\])
Dose Escalation and Expansion: Duration of Response (DoR) Time from first documented response until disease progression or death (approximately 1 year). Time from first documented response until the date of relapse or death.
Dose Escalation and Expansion: Objective Response Rate (ORR) From first dose of BH-30236 until disease progression (up to approximately 1 year) 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 \[PR\]).
Dose Escalation and Expansion: Maximum observed blood concentration (Cmax) of BH-30236. Evaluation performed in Cycle 1 (cycle duration is 28 days). Blood samples for PK analyses will be collected at predetermined time points and analyzed.
Dose Escalation and Expansion: Concentration before dose at steady state (Ctrough). Evaluation performed in all treatment cycles up to one year (cycle duration is 28 days). Blood samples for PK analyses will be collected at predetermined time points and analyzed.
Trial Locations
- Locations (10)
City of Hope Medical Center
🇺🇸Duarte, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
The Ohio State University Wexner Medical Center - James Cancer Hosp
🇺🇸Columbus, Ohio, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
The University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Wisconsin Clinical Science Center
🇺🇸Madison, Wisconsin, United States