The backbone of therapy of acute myeloid leukemia (AML) is based on cytarabine, a drug which, although used as the first-line treatment for AML since 1970s and as a second-line treatment for acute lymphoblastic leukemia (ALL), is associated with severe side effects, such as cerebellar toxicity and bone marrow suppression. Hence, while the incidence of AML increases with age, doses of cytarabine are significantly attenuated or the drug is entirely excluded from the regimen used in older adults due to its potential toxicities, particularly in individuals with hepatic or renal dysfunction.

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BST-236 is a novel chemotherapy agent, a pro-drug of cytarabine, designed to enable delivery of high cytarabine doses to leukemia cells with lower systemic exposure to the free drug. BST-236 metabolizes to cytarabine in the blood and in the cells while avoiding exposure to the high and toxic peak levels of free cytarabine, and therefore enabling relative sparing of normal tissues. 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 cannot be treated by effective doses of chemotherapy. The aim of this study was to evaluate the safety and optimal dose of BST-236 in refractory/relapsed or medically unfit newly-diagnosed acute leukemia patients.

 

Results from the ongoing study were recently presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, by Dr. Jessica K. Altman M.D., Professor, Medicine, Feinberg School of Medicine of Northwestern University and Lead Study Investigator.

 

Presentation name: “Durable Remissions and Increased Overall Survival in AML Patients Deemed Unfit for Standard Intensive Chemotherapy Achieved with High-Dose BST-236 (Aspacytarabine) Induction and Consolidation” 

 

​Key presentation highlights:

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• 61 patients treated to date across the completed Phase 1/2a and ongoing Phase 2b studies, 39 received the recommended Phase 2 dose of 4.5 g/m2/d, which contains 3 g/m2/d cytarabine. Of them, 35 patients were evaluable for safety and overall survival (OS) analysis, and 31 were evaluable for response analysis

• Baseline patient characteristics include a median age 75, 37% of patients (n=13) ECOG 2, 51% of patients (n=18) with secondary AML, 20% with prior hypomethylating agents (HMA) treatment (n=7) and 40% (n=14) adverse ELN

• Repeated courses of aspacytarabine were well-tolerated in older patients and those deemed unfit for chemotherapy

• Observed adverse events were mainly “on-target” with no cerebellar toxicity, severe mucositis, or renal failure observed

• Complete remission (CR) rates were 32% across all evaluable patients, 43% in de novo AML patients, 24% in secondary AML patients, 14% in patients with prior HMA therapy, and 33% in adverse ELN score patients

• Complete hematological recovery was observed in all CRs with a median time to recovery of 27.5 days

• 57% of evaluable CRs were minimal residual disease negative (MRD(-))

• Duration of response (DOR) was not reached at the end of patient follow up at 12 months, median OS of responders was not reached at 24 months

• Median OS of de novo patients was not reached at 24 months; Median OS of secondary AML patients was 6.8 months

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A multi-center Phase 2b trial in the US and Israel is ongoing and is currently enrolling newly-diagnosed AML patients who are unfit for standard chemotherapy, including patients with AML developed from myelodysplastic syndrome (MDS) or following previous exposure to chemotherapy, radiotherapy, or hypomethylating agents. 

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If you consider participating in a clinical trial, you should be aware that:

Our clinical trials run according to the Principles of Good Clinical Practice (GCP) are under the supervision of the required ethics committees whose mission is to ensure the safety and welfare of study participants. 
Clinical trials can only be conducted if all possible precautions have been taken to protect patient safety. Furthermore, the investigational drug is only tested if there is a real possibility of therapeutic benefit that needs to be evaluated. 
Participation in a clinical trial may give a patient the opportunity, especially when there are no existing treatments or they are ineffective or poorly tolerated, to benefit from innovative treatment. 
The potential adverse events are part of the information given by the physician to patients invited to participate in a trial. Patients are given time to reflect. In the event that a patient wishes to enter a trial, he or she signs a free and informed consent form stating that relevant information on the study, its procedures, risks and constraints have been made known to him or her. 
Patients may decide at any time to withdraw from the trial.

 

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