A Study of BH-30236 in Relapsed/ Refractory Acute Myelogenous Leukemia and Higher Risk Myelodysplastic Syndrome

a study on Leukemia Preleukemia Myelodysplastic Syndrome Acute Myeloid Leukemia

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Los Angeles 5368361, California 5332921 and other locations
Dates
study started
study ends around
Principal Investigator
by Gary J. Schiller, MD
Headshot of Gary J. Schiller
Gary J. Schiller

Description

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.

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)

Details

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 as a monotherapy or in combination with venetoclax, in adult participants with R/R AML or HR-MDS.

The study consists of three parts: Phase 1, Part 1 Dose Escalation - Monotherapy, Phase 1, Part 2 Dose Escalation - Combination with Venetoclax, and Phase 1b Dose Expansion.

Phase 1, Part 1 Dose Escalation - Monotherapy is anticipated to enroll approximately 50 participants 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, Part 2 Dose Escalation - Combination with Venetoclax is anticipated to enroll approximately 48 participants 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 a Bayesian optimal interval (BOIN) design dose escalation, where participants will receive ascending doses of BH-30236 to determine the recommended RDEs.

Phase 1b Dose Expansion will enroll approximately 72 participants to evaluate the safety, tolerability, and preliminary anti-leukemic activity of BH-30236 as a monotherapy or in combination with venetoclax at selected RDEs determined in Phase 1 Dose Escalation.

Keywords

Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute, Preleukemia, Myelodysplastic Syndromes, Refractory Acute Myeloid Leukemia, Myeloid Leukemia, venetoclax

Eligibility

You can join if…

Open to people ages 18 years and up

  • ≥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.

You CAN'T join if...

  • 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.

Locations

  • University of California Los Angeles accepting new patients
    Los Angeles 5368361 California 5332921 90095 United States
  • City of Hope Medical Center accepting new patients
    Duarte 5344147 California 5332921 91010 United States

Lead Scientist at UCLA

  • Gary J. Schiller, MD
    Professor-in-Residence, Medicine. Authored (or co-authored) 169 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
BlossomHill Therapeutics
Links
Sign up for this study
ID
NCT06501196
Phase
Phase 1 research study
Study Type
Interventional
Participants
Expecting 170 study participants
Last Updated
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