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

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

Study Overview

• Status: Recruiting
• Conditions: AML, Adult
• Intervention / Treatment: Drug: BST-236; Drug: venetoclax

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Northwestern Memorial Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Abhishek Maiti, MD; Phone Number: 833-974-4697; Email: AMaiti@mdanderson.org
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; BSR-236 + venetoclax

Drug: BST-236; 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; Drug: venetoclax; 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; Other Names: Venclevta

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: BioSight Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Anticipated): August 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: August 14, 2022
• First Submitted That Met QC Criteria: August 14, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 2, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: BST005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No