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

AML, Adult Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05503355
• Other study ID #: BST005
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 17, 2022
• Est. completion date: December 1, 2025

Study information

• Verified date: August 2022
• Source: BioSight Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 1, 2025
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• AML, Adult

Intervention

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
• 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

Locations

Country	Name	City	State
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
BioSight Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity and maximal tolerated dose for part 2		Up to day 42
Primary	In part 2:	Complete remission rate	Up to day 42 of second induction