A Phase I/IIa, open-label, uncontrolled study to evaluate the safety and efficacy of Astarabine (BST-236) as single agent in patients with refractory or relapsed Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) disease
This is prospective, Phase I/IIa, open-label, uncontrolled, single-center, single arm study to evaluate the safety and efficacy of Astarabine given intravenously (I.V.) in escalated doses for 6 days for cycle in patients with relapsed or refractory AML or ALL who are more than 18 years of age. Patients will be screened for eligibility based on existing records and/or specific laboratory examinations performed for the screening process. Patients will be gradually enrolled into 4 subsequent cohorts of escalating drug doses: Cohort # Astarabine Dose Number of Patients 1. 0.5 gr/m2 (0.3 age\>50) 3 2. 1.5 gr/m2 (0.8age\>50) 3 3. 3.0 gr/m2 (1.5 age\>50) 3 4. 4.5 gr/m2 (2.3 age\>50) 6 5. 4.5 gr/m2 (no age limit) 3 up to 6 6. 6 gr/m2 (no age limit) 3 up to 6 Maximal tolerated dose (MTD) will be defined in case 2 subjects will experience a dose limiting toxicity (DLT)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Cohort # Astarabine Dose Number of Patients 1. 0.5 gr/m2 (0.3 age\>50) 3 2. 1.5 gr/m2(0.8age\>50) 3 3. 3.0 gr/m2(1.5 age\>50) 3 4. 4.5 gr/m2(2.3 age\>50) 6 5. 4.5 gr/m2 (no age limit) 3 up to 6 6. 6 gr/m2 (no age limit) 3 up to 6 Total number of patients: up to 24
Rambam medical center hematology department
Haifa, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
Maximal tolerated dose (MTD)
Time frame: 90 days
Dose limiting Toxicity (DLTs)
Any ≥ grade 3 non-hematologic toxicity (excluding alopecia, hypersensitivity) Grade 3 nausea and vomiting if it occurs despite maximal (5HT antagonist and corticosteroid) antiemetic therapy, and if hydration is required for \>24 hours. Grade 3 diarrhea despite patient compliance with loperamide therapy.
Time frame: within 90 days
safety and tolerability expressed by any grade adverse events (AEs)
Time frame: within 90 days
PharmacoKintetics (PK): maximum plasma concentration (Cmax)
Time frame: PK studies will be performed up to 8 days at the following time points: 0', 15', 30', 60', 90', 120', 240', 360', and 600' of days: 1 to 6 and 24 hours and 48 hours after last Astarabine administration (days 7 - 8)
response rate: complete remission + partial remission (CR + PR)
using the revised recommendations of the international working group for diagnosis, standardization of response criteria, tratment outcome and reporting stanndadarts fro therapeutic trials in acute myeloid leukemia
Time frame: within 90 days
Phrmacokinetics (PK): area under the curve (AUC) versus time curve
Time frame: PK studies will be performed up to 8 days at the following time points: 0', 15', 30', 60', 90', 120', 240', 360', and 600' of days: 1 to 6 and 24 hours and 48 hours after last Astarabine administration (days 7 - 8)
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