BH-30236: BH-30236 will be provided as either a 5 mg, 15 mg or 30 mg tablet. Participants will take BH-30236 tablets orally depending on their dose level assignment.
Venetoclax: Venetoclax will be provided as 10 mg, 50 mg or 100 mg tablets. Participants will take venetoclax orally per label instructions.
Study 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, Part 1 Dose Escalation - Monotherapy 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, Part 1 Dose Escalation - Monotherapy.
Phase 1, Part 2 Dose Escalation - Combination with Venetoclax will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of BH-30236 administered as a combination therapy with venetoclax. Approximately 48 participants may be enrolled in Phase 1, Part 2 Dose Escalation - Combination with Venetoclax.
Phase 1b (Dose Expansion) will follow Phase 1 to further understand the relationships among dose, exposure, toxicity, tolerability, and clinical activity. Up to 72 participants may be enrolled in Phase 1b of the study as a monotherapy or in combination with venetoclax.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion criteria:
* ≥18 years.
* Diagnosis of relapsed/refractory acute myelogenous leukemia (R/R) AML or higher-risk myelodysplastic syndrome (HR-MDS) with ≥5% bone marrow blast at time of inclusion.
* Prior treatment history must include 1-5 prior lines of therapy.
* ECOG performance status ≤2.
* Adequate organ function evidenced by the following laboratory values:
* Hepatic: Transaminase levels aspartate aminotransferase \[AST\]/ alanine transaminase \[ALT\] ≤ 2.5 × upper limit of normal (ULN). In cases of liver involvement by AML or MDS, AST and ALT \< 5.0 × ULN is acceptable. Total bilirubin ≤ 1.5 × ULN in the absence of documented Gilbert's disease.
* Renal: Measured or calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula)
The above are a summary, other inclusion criteria details may apply.
Exclusion Criteria:
* 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.
Primary outcome measure(s)
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.
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 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).
Trial sites (13)
Facility
City
Region
Status
City of Hope Medical Center
Duarte
California
Recruiting
University of California Los Angeles
Los Angeles
California
Recruiting
Stanford Cancer Center
Palo Alto
California
Recruiting
Sylvester Comprehensive Cancer Center
Miami
Florida
Recruiting
Moffitt Cancer Center
Tampa
Florida
Recruiting
Northwestern Medicine - Northwestern Memorial Hospital Galter Pavilion
Chicago
Illinois
Recruiting
Roswell Park Cancer Institute
Buffalo
New York
Recruiting
Memorial Sloan Kettering Cancer Center
New York
New York
Recruiting
The Ohio State University Wexner Medical Center - James Cancer Hosp
Columbus
Ohio
Recruiting
Sarah Cannon Research Institute
Nashville
Tennessee
Recruiting
The University of Texas M.D. Anderson Cancer Center
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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