Efficacy and Safety of BST-236 in Newly Diagnosed Acute Myeloid Leukemia Patients, Unfit for Standard Induction Therapy

NCT ID: NCT03435848

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-14
• Study Completion Date: 2023-03-16

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 induction chemotherapy due to advanced age or comorbidities. The Complete Remission (CR) rate following treatment with BST-236 will be compared to the CR rate reported in historical data in a similar population.

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 cytarabine to medically-unfit or older adults who otherwise cannot be treated with standard cytarabine therapy. This study aims to validate this hypothesis.

The study is an open-label, single arm, single agent, multi-center study in adults with newly diagnosed AML who are unfit for standard therapy. The patients will receive up to 4 courses of six-days treatment with intravenous BST-236; 1 or 2 induction courses followed by 1 to 2 consolidation courses. The study participation will be 52 weeks including treatment and follow-up periods. An additional 1 year post study follow-up for the evaluation of survival is optional.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BST-236

BST-236 Intravenous, 4.5 g/m2/d or 2.5 g/m2/d, for 6 days

Group Type: EXPERIMENTAL

BST-236

Intervention Type: DRUG

1 to 4 courses

Interventions

BST-236

1 to 4 courses

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult ≥18 years of age

2. 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

1. de-novo AML or

2. AML secondary to MDS or

3. 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

3. Not eligible for standard induction chemotherapy;

1. Age ≥75 years or

2. 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

4. Creatinine clearance (estimated by the Cockroft-Gault (C-G) or measured by 24 hours urine collection) ≥45 mL/min

5. Liver enzymes (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 times the upper limits of normal (ULN)

6. Total bilirubin ≤1.5 x ULN unless due to known history of Gilbert's disease

7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening

8. 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

9. Women of reproductive potential must have a negative serum pregnancy test within 48 hours of the first day of any BST-236 treatment course

10. 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)

11. 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

12. Patient must be able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria

1. Patient has relapsed or refractory AML

2. Patient has acute promyelocytic leukemia

3. Any previous treatment for AML (except for hydroxyurea or up to one treatment course with hypomethylating agents (HMA))

4. 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

5. Previous use (prior to study initiation) of drugs containing cytarabine as an active ingredient

6. Use of any HMA for the treatment of MDS within 30 days of study Day 1

7. 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

8. 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

9. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)

10. 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

11. 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)

12. Active malignant disease other than AML

13. Leptomeningeal/central nervous system involvement of AML

14. Myeloid sarcoma as a sole manifestation of AML

15. Surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) in the 14 days prior to BST-236 administration

16. Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 4 congestive heart failure

17. Shortness of breath requiring continuous oxygen treatment for at least 15 hours per day in chronically hypoxemic patients

18. History of allergic reactions attributed to compounds of similar chemical composition as BST-236 and/or cytarabine

19. Life expectancy shorter than 3 months attributed to any known medical condition other than AML

20. 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioSight Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Augusta University Georgia Cancer Center

Augusta, Georgia, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Franciscan Physician Network Oncology and Hematology Specialists

Indianapolis, Indiana, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Memorial Sloan Kettering Cancer Center New York

New York, New York, United States

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

Columbus, Ohio, United States

Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Hollings Cancer Center

Charleston, South Carolina, United States

Baylor Scott & White Research Institute Dallas Texas

Dallas, Texas, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

West Virginia University

Morgantown, West Virginia, United States

Soroka University Medical Center

Beersheba, , Israel

Rambam medical center hematology department

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Countries

United States; Israel

References

Altman JK, Zuckerman T, Koprivnikar J, McCloskey J, Kota V, Keng M, Frankfurt O, Abaza Y, Bixby DL, Emadi A, Burch M, Bhatnagar B, Luger SM, Percival ME, Wolach O, Craig M, Ganzel C, Roboz G, Levi I, Gourevitch A, Flaishon L, Tessler S, Blumberg C, Gengrinovitch S, Ben Yakar R, Rowe JM. Aspacytarabine for the treatment of patients with AML unfit for intensive chemotherapy: a phase 2 study. Blood Adv. 2023 Dec 26;7(24):7494-7500. doi: 10.1182/bloodadvances.2023010943.

Reference Type: DERIVED

PMID: 37903324 (View on PubMed)

Other Identifiers

BST002

Identifier Type: -

Identifier Source: org_study_id