Combining BST-236 and venetoclax for treating unfit patients with newly diagnosed AML

A Phase I/II Dose Escalation and Expansion Study of BST-236 Plus Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia Unfit for Intensive Induction Chemotherapy

This study is testing a new combination of two medications, BST-236 and venetoclax, to see if it can help adults with newly diagnosed Acute Myeloid Leukemia who aren't fit for standard treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 90 Years
• Sex: All
• Sponsor: BioSight Ltd. (industry)
• Drugs / interventions: chemotherapy
• Locations: 3 sites (Chicago, Illinois and 2 other locations)
• Trial ID: NCT05503355 on ClinicalTrials.gov

What this trial studies

This clinical trial is an open-label, multi-center study designed to evaluate the safety and efficacy of BST-236 in combination with venetoclax in adult patients who are newly diagnosed with Acute Myeloid Leukemia (AML) and are unfit for standard therapy. The study is divided into two parts: the first part will determine the maximum tolerated dose of the combination treatment, while the second part will expand on this dose to further assess its efficacy and safety. All participants will undergo two induction courses with both treatments, followed by up to three maintenance courses with BST-236 alone if they respond positively. Patients will be monitored for one year during the study and an additional year in post-study follow-up.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with newly diagnosed AML who are unfit for standard induction chemotherapy.

Not a fit: Patients with acute promyelocytic leukemia or those who have previously received treatment for AML may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with AML who are not eligible for standard chemotherapy.

How similar studies have performed: While this specific combination has not been extensively tested, similar approaches in treating AML have shown promise in other studies.

Eligibility criteria

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

Where this trial is running

Chicago, Illinois and 2 other locations

• Northwestern Memorial Hospital — Chicago, Illinois, United States (NOT_YET_RECRUITING)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)
• University of Virginia Cancer Center — Charlottesville, Virginia, United States (RECRUITING)

Conditions: AML, Adult