Status:
COMPLETED
Efficacy and Safety of BST-236 in Newly Diagnosed Acute Myeloid Leukemia Patients, Unfit for Standard Induction Therapy
Lead Sponsor:
BioSight Ltd.
Conditions:
Acute Myeloid Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
The purpose of this study is to assesses the benefit, safety, and pharmacokinetics (PK) of BST-236 in patients with newly-diagnosed Acute Myeloid Leukemia (AML) who are not eligible for standard induc...
Detailed Description
BST-236 is a cytarabine pro drug designed to release cytarabine inside the target cells with reduced systemic exposure to free cytarabine. As such, BST-236 may enable delivery of high doses of cytarab...
Eligibility Criteria
Inclusion
- Adult ≥18 years of age
- AML according to the 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: ≥20% blasts in peripheral blood or marrow
- de-novo AML or
- AML secondary to MDS or
- AML secondary to exposure to potentially leukemogenic therapies or agents (e.g. radiation therapy, alkylating agents, topoisomerase II inhibitors) with the primary malignancy in remission for at least 2 years
- Not eligible for standard induction chemotherapy;
- Age ≥75 years or
- Age ≥18 years with at least one of the following comorbidities:
- i. Clinically significant heart or lung comorbidities, as reflected by at least one of:
- Left ventricular ejection fraction (LVEF) ≤50%
- Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected
- Forced expiratory volume in 1 second (FEV1) ≤65% of expected ii. Chronic stable angina or congestive heart failure controlled with medication iii. Other contraindication(s) to anthracycline therapy (must be documented) iv. Other comorbidity that the Investigator judges as incompatible with intensive remission induction chemotherapy, which must be documented
- Creatinine clearance (estimated by the Cockroft-Gault (C-G) or measured by 24 hours urine collection) ≥45 mL/min
- Liver enzymes (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 times the upper limits of normal (ULN)
- Total bilirubin ≤1.5 x ULN unless due to known history of Gilbert's disease
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
- Prepared and able to give written (signed and dated) informed consent, which includes compliance with study requirements and restrictions prior to admission to the study
- Women of reproductive potential must have a negative serum pregnancy test within 48 hours of the first day of any BST-236 treatment course
- Women or men of reproductive potential must use (or have his/her partner use) two forms of effective birth control methods starting from 1 month prior to screening and until 3 months following the last BST-236 administration day (acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptives, contraceptive patch, long-acting injectable contraceptives, partner's vasectomy, or double-barrier method condom or diaphragm with spermicide)
- Patient must voluntarily sign and date an ICF, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures
- Patient must be able to adhere to the study visit schedule and other protocol requirements
Exclusion
- Patient has relapsed or refractory AML
- Patient has acute promyelocytic leukemia
- Any previous treatment for AML (except for hydroxyurea or up to one treatment course with hypomethylating agents (HMA))
- Patient has history of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation
- Previous use (prior to study initiation) of drugs containing cytarabine as an active ingredient
- Use of any HMA for the treatment of MDS within 30 days of study Day 1
- Participation in a previous clinical trial and/or use of an investigational drug within 90 days or at least 5 half-lives of tested drug (whichever is longer) of initial screening assessment
- Peripheral White Blood Cell (WBC) count \>30,000 /µL in the 48 hours prior to first BST-236 dose administration. Hydroxyurea administration or leukapheresis is permitted to meet this criterion
- 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 laboratory abnormalities or psychiatric illness that may preclude safe and complete study participation based on the Investigator's judgment
- Diagnosis of malignant disease within the previous 12 months (excluding basal cell carcinoma of the skin without complications, "in-situ" carcinoma, or other local malignancy excised or irradiated with a high probability of cure and not treated with chemotherapy)
- Active malignant disease other than AML
- Leptomeningeal/central nervous system involvement of AML
- Myeloid sarcoma as a sole manifestation of AML
- Surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) in the 14 days prior to BST-236 administration
- Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 4 congestive heart failure
- Shortness of breath requiring continuous oxygen treatment for at least 15 hours per day in chronically hypoxemic patients
- History of allergic reactions attributed to compounds of similar chemical composition as BST-236 and/or cytarabine
- Life expectancy shorter than 3 months attributed to any known medical condition other than AML
- Active/chronic Hepatitis B Virus (HBV) infection (based on positive surface antigen (HBsAg)), Hepatitis C Virus (HCV) infection (HCV) (based on positive HCV antibody (Ab)), or Human Immunodeficiency Virus (HIV)-1 or HIV-2 (based on positive HIV antibody)
Key Trial Info
Start Date :
August 14 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 16 2023
Estimated Enrollment :
66 Patients enrolled
Trial Details
Trial ID
NCT03435848
Start Date
August 14 2018
End Date
March 16 2023
Last Update
July 27 2023
Active Locations (16)
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1
Augusta University Georgia Cancer Center
Augusta, Georgia, United States, 30912
2
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
3
Franciscan Physician Network Oncology and Hematology Specialists
Indianapolis, Indiana, United States, 46237
4
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109