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

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ClinicalTrials.gov Identifier: NCT04749355
Recruitment Status : Not yet recruiting
First Posted : February 11, 2021
Last Update Posted : February 15, 2021
Sponsor:
Information provided by (Responsible Party):
BioSight Ltd.

Tracking Information
First Submitted Date  ICMJE February 7, 2021
First Posted Date  ICMJE February 11, 2021
Last Update Posted Date February 15, 2021
Estimated Study Start Date  ICMJE March 14, 2021
Estimated Primary Completion Date August 14, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2021)
  • CR rate [ Time Frame: To be assessed 5 months after the last patient was enrolled to the study ]
    In AML patients -The proportion of patients who achieve a CR per the IWG 2006 Criteria
  • Overall response rate (ORR) [ Time Frame: To be assessed 5 months after the last patient was enrolled to the study ]
    In MDS patients -Overall response rate (ORR), defined as the proportion of patients who achieve a CR or PR per proposal for modification of the International Working Group (IWG) criteria for MDS, 2006
Original Primary Outcome Measures  ICMJE
 (submitted: February 7, 2021)
  • For AML patients -CR rate [ Time Frame: To be assessed 5 months after the last patient was enrolled to the study ]
    The proportion of patients who achieve a CR per the IWG 2006 Criteria
  • For MDS patients [ Time Frame: To be assessed 5 months after the last patient was enrolled to the study ]
    Overall response rate (ORR), defined as the proportion of patients who achieve a CR or PR per proposal for modification of the International Working Group (IWG) criteria for MDS, 2006
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS
Official Title  ICMJE A Phase 2, Open-Label, Single Arm, Multi-Center Study to Assess the Efficacy and Safety of BST-236 as a Single Agent in Adults Unfit for Intensive Chemotherapy With Relapsed or Refractory AML or Higher-Risk Myelodysplastic Syndromes
Brief Summary

An open label multi center study to assess the safety and efficacy of BST-236 as single agent in adult patients unfit for standard therapy with Acute Myeloid Leukemia (AML) or higher-risk (HR) Myelodysplastic Syndromes (MDS) who fail to respond or relapsed following first line therapy.

Approximately 20 adult patients with relapsed and/or refractory AML and approximately 20 adult patients with relapsed and/or refractory HR MDS, will be enrolled into the study.

Patients will be treated with 1-2 induction courses and 2-4 maintenance courses. All patients will be followed for 1 year in the study and additional 1 year post study follow-up.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open-label, multi-center, single arm, single agent study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • AML, Adult
  • MDS
  • Relapse/Recurrence
  • Refractory Acute Myeloid Leukemia
Intervention  ICMJE Drug: BST-236
BST-236 is a conjugate of cytarabine and asparagine, provided as a sterile lyophilized powder for IV administration
Other Name: Aspacytarabine
Study Arms  ICMJE Experimental: BST-236
BST-236 Intravenous, 4.5 g/m^2/d or 2.3 g/m^2/d, for 6 days
Intervention: Drug: BST-236
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2021)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 14, 2024
Estimated Primary Completion Date August 14, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Liat Flaishon +97236568669 Liat@Biosight-pharma.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04749355
Other Study ID Numbers  ICMJE BST004
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party BioSight Ltd.
Study Sponsor  ICMJE BioSight Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account BioSight Ltd.
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP