Clinical trial NCT06501196: A Study of BH-30236 in Relapsed/ Refractory Acute Myelogenous Leukemia and Higher Risk Myelodysplastic Syndrome
Official title: A Phase 1/1b Open-Label, Dose Escalation, First-in- Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-leukemic Activity of the Orally Available CDC-Like Kinase (CLK) Inhibitor, BH-30236, in Adults With Relapsed or Refractory Acute Myelogenous Leukemia (R/R AML) or Higher-Risk Myelodysplastic Syndrome (HR-MDS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Refractory Acute Myeloid Leukemia
Lead sponsor: BlossomHill Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-07-15
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 outcomes:
measure: Dose Escalation: Frequency of dose limiting toxicities (DLTs)
timeFrame: Dose-limiting toxicities are collected during the first treatment cycle (28 days)
measure: 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
timeFrame: From first dose until 28 days after last dose of BH-30236
measure: Dose Expansion: Composite Complete Remission (CR) Rate
timeFrame: From first dose of BH-30236 until disease progression (up to approximately 1 year)
Secondary outcomes:
measure: Dose Escalation and Expansion: Maximum observed blood concentration (Cmax) of BH-30236.
timeFrame: Evaluation performed in Cycle 1 (cycle duration is 28 days).
measure: Dose Escalation: Area under the blood concentration time curve (AUC) of BH-30236.
timeFrame: Evaluation performed in Cycle 1 (cycle duration is 28 days).
measure: Dose Escalation and Expansion: Concentration before dose at steady state (Ctrough).
timeFrame: Evaluation performed in all treatment cycles up to one year (cycle duration is 28 days).
measure: Dose Escalation and Expansion: Objective Response Rate (ORR)
timeFrame: From first dose of BH-30236 until disease progression (up to approximately 1 year)
measure: Dose Escalation and Expansion: Duration of Response (DoR)
timeFrame: Time from first documented response until disease progression or death (approximately 1 year).
measure: Dose Escalation and Expansion: Time to remission (TTR)
timeFrame: From first dose of BH-30236 until complete remission, disease progression or death (approximately 1 year).
measure: Dose Escalation and Expansion: Relapse-free Survival (RFS)
timeFrame: From first dose of BH-30236 until disease progression, death, or initiation of a new anti-leukemic therapy (approximately 1 year).
measure: Dose Escalation and Expansion: Measurable Residual Disease (MRD)
timeFrame: From time of first dose until discontinuation of BH-30236 (approximately 1 year).
measure: Dose Escalation and Expansion: Measurement of the change in RNA alternative splicing markers on BH-30236 treatment
timeFrame: From time of first dose until discontinuation of BH-30236 (approximately 1 year).
measure: 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
timeFrame: Time from first documented response until disease progression or death (approximately 1 year)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center - James Cancer Hosp
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Clinical Science Center
state: Wisconsin
Study officials:
affiliation: BlossomHill Therapeutics, Inc.
name: Sponsor Contact
role: STUDY_DIRECTOR
References: