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

Acute Myeloid Leukemia Clinical Trial

— ELPIS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03435848
• Other study ID #: BST002
• Status: Completed
• Phase: Phase 2
• Start date: August 14, 2018
• Est. completion date: March 16, 2023

Study information

• Verified date: July 2023
• Source: BioSight Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: March 16, 2023
• Est. primary completion date: March 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• BST-236
1 to 4 courses

Locations

Country	Name	City	State
Israel	Soroka University Medical Center	Be'er Sheva
Israel	Rambam medical center hematology department	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Rabin Medical Center	Petach Tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Augusta University Georgia Cancer Center	Augusta	Georgia
United States	Hollings Cancer Center	Charleston	South Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute	Columbus	Ohio
United States	Baylor Scott & White Research Institute Dallas Texas	Dallas	Texas
United States	Franciscan Physician Network Oncology and Hematology Specialists	Indianapolis	Indiana
United States	West Virginia University	Morgantown	West Virginia
United States	Memorial Sloan Kettering Cancer Center New York	New York	New York
United States	Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
BioSight Ltd.

Countries where clinical trial is conducted

United States,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Remission	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)	Day 28-35 of induction/re induction course