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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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AML, Adult

Intervention / Treatment
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* Drug: BST-236
* Drug: venetoclax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult ≥18 years of age Diagnosis of AML (de-novo AML or AML secondary to MDS or secondary to exposure to potentially leukemogenic therapies or agents) Not eligible for standard induction chemotherapy Peripheral white blood cell (WBC) count of <25,000/μL Creatinine clearance ≥45 mL/min AST and/or aALT ≤2.5 X ULN) Total bilirubin ≤1.5 x ULN ECOG PS of: 0 to 2 for patients ≥75 years of age 0 to 3 for patients <75 years of age Women of reproductive potential must have a negative serum pregnancy test within 48 hours of Study Day 1 Exclusion Criteria: Patient has acute promyelocytic leukemia Any previous treatment for AML Patient has a known history of myeloproliferative neoplasm (MPN) Patient has known active central nervous system (CNS) involvement with AML Use of an investigational drug within 5 half-lives (or 30 days in case the half-life is unknown) prior to Study Day 1 Previous BM/stem cell transplantation (SCT) Previous treatment for MDS with cytarabine, hypomethylating agents, or venetoclax For Part 1 only - use of known strong or moderate CYP3A inducers within 7 days prior to Study Day 1 Patient has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or starfruit within 3 days prior to Study Day 1 Patient has a malabsorption syndrome or other condition that precludes enteral route of drug administration Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment) 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. Diagnosis of malignant disease other than AML within the previous 12 months Diagnosis of myeloid sarcoma as a sole manifestation of AML Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) Class IV CHF History of allergic reactions attributed to compounds of similar chemical composition as BST-236 and/or cytarabine and/or venetoclax. Surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) in the 14 days prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>BSR-236 + venetoclax | Drug: BST-236<br>* In part 1: During the induction (in combination with venetoclax), the BST-236 doses are: In cohort 1 - 2.3 g/m2/d X6 days In cohort 2 - 2.3 g/m2/d X6 days In cohort 3 - 4.5 g/m2/d X6 days In cohort 4 - 4.5 g/m2/d X6 days In cohort 5 - 4.5 g/m2/d X6 days In part 1: During maintenances (for responding patients) the BST-236 dose- 4.5 g/m2/d X6 days In part 2, the dose chosen as safe and efficacious for induction in part 1 will be used<br>Drug: venetoclax<br>* In part 1: During the induction (in combination with BST-236), the venetoclax doses are: In cohort 1 - 200 mg QD X 7 days In cohort 2 - 400 mg QD X 7 days In cohort 3 - 200 mg QD X 7 days In cohort 4 - 400 mg QD X 7 days In cohort 5 - 200 mg QD X 14 days In part 2, the dose chosen as safe and efficacious for induction in part 1 will be used<br>* Other names: Venclevta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity and maximal tolerated dose for part 2 |  | Up to day 42 | 
| In part 2: | Complete remission rate | Up to day 42 of second induction |