Clinical Trials /

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

NCT03435848

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety of BST-236 in Newly Diagnosed Acute Myeloid Leukemia Patients, Unfit for Standard Induction Therapy
  • Official Title: A Phase 2b Open-Label, Single Arm, Multi-Center Study to Assess the Efficacy and Safety of BST-236 as a Single Agent in Adults With Newly-Diagnosed Acute Myeloid Leukemia (AML), Not Eligible for Standard Induction Therapy

Clinical Trial IDs

  • ORG STUDY ID: BST002
  • NCT ID: NCT03435848

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
BST-236BST-236

Purpose

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.

Detailed Description

      BST-236 is a cytarabine pro drug designed to release cytarabine inside the target cells with
      reduced systemic exposure to free cytarabine. As such, BST-236 may enable delivery of high
      doses of cytarabine to medically-unfit or older adults who otherwise cannot be treated with
      standard cytarabine therapy. This study aims to validate this hypothesis.

      The study is an open-label, single arm, single agent, multi-center study in adults with newly
      diagnosed AML who are unfit for standard therapy. The patients will receive up to 4 courses
      of six-days treatment with intravenous BST-236; 1 or 2 induction courses followed by 1 to 2
      consolidation courses. The study participation will be 52 weeks including treatment and
      follow-up periods. An additional 1 year post study follow-up for the evaluation of survival
      is optional.
    

Trial Arms

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

Eligibility Criteria

        Inclusion Criteria:

          1. Adult ≥18 years of age

          2. 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

               1. de-novo AML or

               2. AML secondary to MDS or

               3. 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

          3. Not eligible for standard induction chemotherapy;

               1. Age ≥75 years or

               2. 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

          4. Creatinine clearance (estimated by the Cockroft-Gault (C-G) or measured by 24 hours
             urine collection) ≥45 mL/min

          5. Liver enzymes (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)
             ≤2.5 times the upper limits of normal (ULN)

          6. Total bilirubin ≤1.5 x ULN unless due to known history of Gilbert's disease

          7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening

          8. Prepared and able to give written (signed and dated) informed consent, which includes
             compliance with study requirements and restrictions prior to admission to the study

          9. Women of reproductive potential must have a negative serum pregnancy test within 48
             hours of the first day of any BST-236 treatment course

         10. Women or men of reproductive potential must use (or have his/her partner use) two
             forms of effective birth control methods starting from 1 month prior to screening 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,
             partner's vasectomy, or double-barrier method condom or diaphragm with spermicide)

         11. Patient must voluntarily sign and date an ICF, approved by an Independent Ethics
             Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any
             screening or study-specific procedures

         12. Patient must be able to adhere to the study visit schedule and other protocol
             requirements

        Exclusion Criteria:

          1. Patient has relapsed or refractory AML

          2. Patient has acute promyelocytic leukemia

          3. Any previous treatment for AML (except for hydroxyurea or up to one treatment course
             with hypomethylating agents (HMA))

          4. 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

          5. Previous use (prior to study initiation) of drugs containing cytarabine as an active
             ingredient

          6. Use of any HMA for the treatment of MDS within 30 days of study Day 1

          7. 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

          8. 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

          9. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing
             signs/symptoms related to the infection without improvement despite appropriate
             antibiotics or other treatment)

         10. 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

         11. 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)

         12. Active malignant disease other than AML

         13. Leptomeningeal/central nervous system involvement of AML

         14. Myeloid sarcoma as a sole manifestation of AML

         15. Surgical procedure, excluding central venous catheter placement or other minor
             procedures (e.g. skin biopsy) in the 14 days prior to BST-236 administration

         16. Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA)
             class 4 congestive heart failure

         17. Shortness of breath requiring continuous oxygen treatment for at least 15 hours per
             day in chronically hypoxemic patients

         18. History of allergic reactions attributed to compounds of similar chemical composition
             as BST-236 and/or cytarabine

         19. Life expectancy shorter than 3 months attributed to any known medical condition other
             than AML

         20. Active/chronic Hepatitis B Virus (HBV) infection (based on positive surface antigen
             (HBsAg)), Hepatitis C Virus (HCV) infection (HCV) (based on positive HCV antibody
             (Ab)), or Human Immunodeficiency Virus (HIV)-1 or HIV-2 (based on positive HIV
             antibody)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Remission
Time Frame:Day 28-35 of induction/re induction course
Safety Issue:
Description: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)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BioSight Ltd.

Trial Keywords

  • Acute Myeloid Leukemia
  • Unfit for standard induction therapy
  • Cytarabine

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