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

NCT03435848 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: BST002
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Unfit for standard induction therapy; Cytarabine

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

BST-236

EXPERIMENTAL

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

Drug: BST-236

Interventions

BST-236 DRUG

1 to 4 courses

BST-236

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BioSight Ltd.: lead

Study Sites (16)

Augusta University Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Franciscan Physician Network Oncology and Hematology Specialists

Indianapolis, Indiana, 46237, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Memorial Sloan Kettering Cancer Center New York

New York, New York, 10065, United States

Location

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

Columbus, Ohio, 43210, United States

Location

Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Baylor Scott & White Research Institute Dallas Texas

Dallas, Texas, 75246, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109-4433, United States

Location

West Virginia University

Morgantown, West Virginia, 26506-9162, United States

Location

Soroka University Medical Center

Beersheba, PO Box 151, Israel

Location

Rambam medical center hematology department

Haifa, 4655202, Israel

Location

Shaare Zedek Medical Center

Jerusalem, P.O.B 3235, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Related Publications (1)

• 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.

  PMID: 37903324 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: February 19, 2018
• Study Start: August 14, 2018
• Primary Completion: March 16, 2023
• Study Completion: March 16, 2023
• Last Updated: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); IL (5)