Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS

Launched by BIOSIGHT LTD. · Feb 7, 2021

Keywords

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ALL

Eligibility criteria

• • 1. Documented diagnosis of MDS, according to World Health Organization (WHO) classification and Revised International Prognostic Scoring System (IPSS-R) overall score ≥ 4.5 Or
• • Diagnosed AML according to the 2016 revision to the WHO classification of myeloid neoplasms and acute leukemia: ≥20% blasts in peripheral blood or bone marrow
• • 2. Adult ≥18 years of age
• • 3. MDS relapse following treatment with azacitidine or decitabine Or
• • MDS failure to achieve complete or partial response or stable disease with hematologic improvement after at least 4 cycles of azacitidine or decitabine, all within the last 1 year Or
• • MDS progression while on azacitidine or decitabine treatment irrespective of the number of cycles the patient has received Or
• • AML relapse after initial CR/CRi/CRh following treatment with: azacitidine, decitabine, Low-Dose Ara-C (LDAC) , venetoclax+HMA, or venetoclax+LDAC Or
• • AML failure to achieve CR, CRh or CRi following at least 4 cycles of azacitidine or decitabine or 2 cycles of venetoclax+HMA or venetoclax+LDAC within the last 1 year.
• • Or
• • AML progression while on azacitidine, decitabine, LDAC, venetoclax+HMA, venetoclax+LDAC, irrespective of the number of cycles the patient has received.
• • 4. Not able to receive an allogeneic bone marrow transplantation (BMT) at the time of study enrolment.
• • 5. Not eligible for intensive chemotherapy;
• • 1. Age ≥75 years Or
• 2. Age ≥18 years with at least one of the following comorbidities:
• 3. Significant heart or lung comorbidities, as reflected by at least one of the following:
• • 4. Left ventricular ejection fraction (LVEF) ≤50%
• • 5. Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected
• • 6. Forced expiratory volume in 1 second (FEV1) ≤65% of expected
• • 7. Chronic stable angina or congestive heart failure controlled with medication
• • 8. Other comorbidity or conditions that the Investigator judges as incompatible with intensive chemotherapy, which must be documented
• • 9. ECOG=2
• • 6. Creatinine clearance (estimated by the Modification of Diet in Renal Disease (MDRD) equation or measured by 24 hours urine collection) ≥45 mL/min
• • 7. Liver enzymes (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 times the upper limits of normal (ULN), unless attributed to leukemia (in AML patients)
• • 8. Total bilirubin ≤3 XULN unless due to Gilbert disease
• • 9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• • 10. Women of reproductive potential must have a negative serum pregnancy test within 48 hours prior to the first day of any BST-236 treatment course
• • 11. Women of reproductive potential must use two forms of effective birth control methods starting from at least 1 month prior to BST-236 first dose 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, or double-barrier method condom or diaphragm with spermicide)
• • 12. Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 3 months following the last dose of study drug
• • 13. Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures
• • 14. Patient must be able to adhere to the study visit schedule and other protocol requirements
• Exclusion Criteria:
• • 1. MDS or AML evolving from a pre-existing myeloproliferative neoplasm (MPN)
• • 2. MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN
• • 3. Acute promyelocytic leukemia
• • 4. Previous treatment for AML or MDS with drugs other than HMA or LDAC or combinations of venetoclax with either HMA or LDAC
• • 5. Previous allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation
• • 6. Participation in a previous clinical trial involving use of an investigational drug within 30 days or at least 5 half-lives of tested drug (whichever is shorter) of study day 1
• • 7. 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
• • 8. Administration of HMA, LDAC, or venetoclax within 14 days prior to Study Day 1
• • 9. Previous treatment with cytarabine at a dose higher than 20 mg/ m2/d
• • 10. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
• • 11. 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
• • 12. Diagnosis of malignant disease (other than AML) 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 systemic or topical chemotherapy)
• • 13. Surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) in the 14 days prior to first BST-236 dose administration
• • 14. History of allergic reactions attributed to compounds of similar chemical composition as BST-236 and/or cytarabine
• • 15. Life expectancy shorter than 3 months attributed to any known medical condition other than AML/MDS
• • 16. In 12 leads ECG, corrected QT interval (QTc)\>480msec or history of QT prolongation or Torsades de pointes