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

NCT05503355 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: BST005
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

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

Conditions

AML, Adult

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

Treatment

EXPERIMENTAL

BSR-236 + venetoclax

Drug: BST-236; Drug: venetoclax

Interventions

BST-236 DRUG

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

Treatment

venetoclax DRUG

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

Also known as: Venclevta

Treatment

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• to 2 for patients ≥75 years of age
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BioSight Ltd.: lead

Study Sites (3)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Virginia Cancer Center

Charlottesville, Virginia, 22903, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2022
• First Posted: August 16, 2022
• Study Start: August 17, 2022
• Primary Completion: August 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 4, 2023

Record last verified: 2022-08

Locations

US (3)