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A Phase I/II Dose Escalation and Expansion Study of BST-236 Plus Venetoclax in Patients With Unfit Newly Diagnosed AML

Phase 1
Recruiting
Conditions
AML, Adult
Interventions
Registration Number
NCT05503355
Lead Sponsor
BioSight Ltd.
Brief Summary

An open label multi centre study to assess the safety and efficacy of BST-236 in combination with venetoclax in adult patients unfit for standard therapy with newly diagnosed Acute Myeloid Leukemia (AML) Part 1 of the study will define the maximal tolerate dose of the combination treatment, while part 2 will expend the chosen dose, to assesses efficacy and safety of this combination.

All patients will receive 2 induction courses with both BST-236 and venetoclax, responding patients will then be followed with up to 3 maintenance courses with BST-236 alone. Patients will be followed for 1 year in the study and additional 1 year in post study follow-up

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
80
Inclusion Criteria
  1. Adult ≥18 years of age

  2. Diagnosis of AML (de-novo AML or AML secondary to MDS or secondary to exposure to potentially leukemogenic therapies or agents)

  3. Not eligible for standard induction chemotherapy

  4. Peripheral white blood cell (WBC) count of <25,000/μL

  5. Creatinine clearance ≥45 mL/min

  6. AST and/or aALT ≤2.5 X ULN)

  7. Total bilirubin ≤1.5 x ULN

  8. ECOG PS of:

    • 0 to 2 for patients ≥75 years of age
    • 0 to 3 for patients <75 years of age
  9. Women of reproductive potential must have a negative serum pregnancy test within 48 hours of Study Day 1

Exclusion Criteria
  1. Patient has acute promyelocytic leukemia
  2. Any previous treatment for AML
  3. Patient has a known history of myeloproliferative neoplasm (MPN)
  4. Patient has known active central nervous system (CNS) involvement with AML
  5. Use of an investigational drug within 5 half-lives (or 30 days in case the half-life is unknown) prior to Study Day 1
  6. Previous BM/stem cell transplantation (SCT)
  7. Previous treatment for MDS with cytarabine, hypomethylating agents, or venetoclax
  8. For Part 1 only - use of known strong or moderate CYP3A inducers within 7 days prior to Study Day 1
  9. Patient has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or starfruit within 3 days prior to Study Day 1
  10. Patient has a malabsorption syndrome or other condition that precludes enteral route of drug administration
  11. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
  12. Any medical or surgical condition, presence of clinical safety laboratory abnormalities, or psychiatric illness that may preclude safe and complete study participation based on the Investigator's judgment.
  13. Diagnosis of malignant disease other than AML within the previous 12 months
  14. Diagnosis of myeloid sarcoma as a sole manifestation of AML
  15. Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) Class IV CHF
  16. History of allergic reactions attributed to compounds of similar chemical composition as BST-236 and/or cytarabine and/or venetoclax.
  17. Surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) in the 14 days prior to enrollment

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TreatmentBST-236BSR-236 + venetoclax
TreatmentvenetoclaxBSR-236 + venetoclax
Primary Outcome Measures
NameTimeMethod
Dose limiting toxicity and maximal tolerated dose for part 2Up to day 42
In part 2:Up to day 42 of second induction

Complete remission rate

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (3)

Northwestern Memorial Hospital

🇺🇸

Chicago, Illinois, United States

The University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

University of Virginia Cancer Center

🇺🇸

Charlottesville, Virginia, United States

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