A Phase I/II Dose Escalation and Expansion Study of BST-236 Plus Venetoclax in Patients With Unfit Newly Diagnosed AML
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- Dose limiting toxicity and maximal tolerated dose for part 2 [Up to day 42]
- In part 2: [Up to day 42 of second induction]
Complete remission rate
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Northwestern Memorial Hospital | Chicago | Illinois | United States | 60611 |
| 2 | University of Virginia Cancer Center | Charlottesville | Virginia | United States | 22903 |
Sponsors and Collaborators
- BioSight Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BST005