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

• ClinicalTrials.gov Identifier: NCT03435848
• Recruitment Status: Active, not recruiting
• First Posted: February 19, 2018
• Last Update Posted: February 8, 2023
• Sponsor: BioSight Ltd.
• Information provided by (Responsible Party): BioSight Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia	Drug: BST-236	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 65 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2b Open-Label, Single Arm, Multi-Center Study to Assess the Efficacy and Safety of BST-236 as a Single Agent in Adults With Newly-Diagnosed Acute Myeloid Leukemia (AML), Not Eligible for Standard Induction Therapy
• Actual Study Start Date: August 14, 2018
• Actual Primary Completion Date: December 1, 2022
• Estimated Study Completion Date: May 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: BST-236; BST-236 Intravenous, 4.5 g/m2/d or 2.5 g/m2/d, for 6 days	Drug: BST-236; 1 to 4 courses

Outcome Measures

Primary Outcome Measures :

1. Complete Remission [ Time Frame: Day 28-35 of induction/re induction course ]
   as BM blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >1.0x 109/L (1,000/μL); platelet count >100 x 109/L (100,000/μL)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, Georgia

Augusta University Georgia Cancer Center

Augusta, Georgia, United States, 30912

United States, Illinois

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

United States, Indiana

Franciscan Physician Network Oncology and Hematology Specialists

Indianapolis, Indiana, United States, 46237

United States, Michigan

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109

United States, New York

Memorial Sloan Kettering Cancer Center New York

New York, New York, United States, 10065

United States, Ohio

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

Columbus, Ohio, United States, 43210

United States, Pennsylvania

Abramson Cancer Center

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

Hollings Cancer Center

Charleston, South Carolina, United States, 29425

United States, Texas

Baylor Scott & White Research Institute Dallas Texas

Dallas, Texas, United States, 75246

United States, Washington

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109-4433

United States, West Virginia

West Virginia University

Morgantown, West Virginia, United States, 26506-9162

Israel

Soroka University Medical Center

Be'er Sheva, Israel, PO Box 151

Rambam medical center hematology department

Haifa, Israel, 4655202

Shaare Zedek Medical Center

Jerusalem, Israel, P.O.B 3235

Rabin Medical Center

Petach Tikva, Israel, 49100

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 6423906

Sponsors and Collaborators

BioSight Ltd.

More Information

• Responsible Party: BioSight Ltd.
• ClinicalTrials.gov Identifier: NCT03435848
• Other Study ID Numbers: BST002
• First Posted: February 19, 2018
• Last Update Posted: February 8, 2023
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by BioSight Ltd.:

Acute Myeloid Leukemia; Unfit for standard induction therapy; Cytarabine

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms