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Information for Clinicians

In spite of the recent encouraging development in the treatment of Acute myeloid leukemia (AML), it is associated with poor outcome in older patients and in patients unfit for standard induction therapy. Cytarabine-based chemotherapy remains as the most effective first-line treatment for AML, however, it is associated with severe side effects, such as cerebellar toxicity, bone marrow suppression, and infections, leading to high treatment-related mortality rates.

Hence, while the incidence of AML increases with age, advanced age and comorbidities may preclude the administration of intensive induction therapy altogether due to its potential toxicities. The outcome in older patients who are unable to receive intensive chemotherapy remains low, especially in patients with AML secondary to myelodysplastic syndrome (MDS) or to prior exposure to chemotherapy, radiotherapy, or hypomethylating agents.

 

BST-236 (INN aspacytarabine) is a novel anti-metabolite, composed of cytarabine covalently bound to asparagine. It acts as a pro-drug of cytarabine, designed to enable delivery of high cytarabine doses to patients with lower systemic exposure to free cytarabine, since BST-236 metabolism and pharmacokinetics result in avoiding exposure to peak toxic levels of the free drug. As such, BST-236 may serve as an ideal therapy for leukemia, particularly for delivering high doses of cytarabine to medically unfit or older adults who otherwise can be given low-dose therapy only. The aim of this study was to evaluate the safety and optimal dose of aspacytarabine in refractory/relapsed or medically unfit patients with acute leukemia.

Biosight recently completed a Phase 1/2a clinical trial to evaluate the safety and efficacy of BST-236 as a mono therapy for AML and ALL, conducted at Rambam Healthcare Center and Tel-Aviv Sourasky Medical Center in Israel under the supervision of Dr. Tsila Zuckerman. Preliminary results indicate that BST-236 is safe and well tolerated, enabling safe delivery of grams of cytarabine to older and unfit patients (median age 79 years). Furthermore, BST-236 treatment achieved high response rates in newly diagnosed de novo AML and secondary AML patients unfit for conventional chemotherapy, including in patients with poor prognosis and patients who progressed to AML from MDS while under treatment with hypomethylating agents. The response was durable and led to significant increase in overall survival.

Final results of the BST-236 Phase 1/2a were presented by Dr. Zuckerman at 59th Annual American Society of Hematology meeting in Atlanta, GA, USA, and published as an Article at the prestigious journal Blood Advances:

>> Zuckerman et al., BST-236 Phase 1/2a article, Blood Advances 2019

 

A multi-center Phase 2b trial in the US and Israel is ongoing, enrolling newly-diagnosed AML patients who are unfit for standard chemotherapy, including secondary AML patients with prior exposure to hypomethylating agents, chemotherapy, and radio therapy.

 

The US study lead is Dr. Jessica K. Altman, Northwestern Memorial Hospital, Chicago IL.

The Israel study lead is Dr. Tsila Zuckerman, Rambam Healthcare Center, Haifa Israel.

Integrated results of the clinical data available to date will be presented on December 7, 2019 by Dr. Jessica K. Altman at the coming ASH meeting in Orlando:

TITLE: Aspacytarabine (BST-236) Is Safe and Efficacious As a Single-Agent, First-Line Therapy for Patients with Acute Myeloid Leukemia Unfit for Standard Chemotherapy. Integrated Results from a Phase 1/2a and an Ongoing Phase 2b

Session Name: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: New Treatment Strategies

Session Date: Saturday, December 7, 2019; Session Time: 12:00 PM - 1:30 PM; Presentation Time: 1:00 PM; Room: Orange County Convention Center, Chapin Theater (W320).

Additional information regarding the study design can be found at: https://clinicaltrials.gov/ct2/show/NCT03435848.

Additional clinical studies in various hematological indications are scheduled to initiate in the coming months.

For further information regarding the phase II study, please contact us via our Contact Form >>

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