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

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ClinicalTrials.gov Identifier: NCT03435848
Recruitment Status : Recruiting
First Posted : February 16, 2018
Last Update Posted : February 27, 2019
Sponsor:
Information provided by (Responsible Party):
BioSight Ltd.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: BST-236 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 14, 2018
Estimated Primary Completion Date : January 1, 2021
Estimated Study Completion Date : April 1, 2021


Arm Intervention/treatment
Experimental: BST-236
BST-236 Intravenous, 4.5 g/m2/d or 2.5 g/m2/d, for 6 days
Drug: BST-236
1 to 4 courses




Primary Outcome Measures :
  1. Complete Remission [ Time Frame: Day 28-35 of induction/re induction course ]
    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)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03435848


Contacts
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Contact: Liat Flaishon, MD +97236568669 liat@biosight-pharma.com

Locations
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United States, Georgia
Augusta University Georgia Cancer Center Recruiting
Augusta, Georgia, United States, 30912
Principal Investigator: Vasmi Kota, MD         
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Olga Frankfurt         
United States, Indiana
Franciscan Physician Network Oncology and Hematology Specialists Recruiting
Indianapolis, Indiana, United States, 46237
Principal Investigator: Nadeem Ikhlaque, MD         
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Dale Bixby, MD         
United States, New York
Memorial Sloan Kettering Cancer Center New York Recruiting
New York, New York, United States, 10065
Principal Investigator: Martin Tallman, MD         
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Recruiting
Columbus, Ohio, United States, 43210
Principal Investigator: Tina Bhatnagar, MD         
United States, Pennsylvania
Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Salina Luger         
United States, South Carolina
Hollings Cancer Center Recruiting
Charleston, South Carolina, United States, 29425
Principal Investigator: Robert Stuart, MD         
United States, Texas
Baylor Scott & White Research Institute Dallas Texas Recruiting
Dallas, Texas, United States, 75246
Principal Investigator: Micah Burch         
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109-4433
Principal Investigator: Mary-Beth Percival, MD         
United States, West Virginia
West Virginia University Recruiting
Morgantown, West Virginia, United States, 26506-9162
Principal Investigator: Michael Craig         
Israel
Soroka University Medical Center Recruiting
Be'er Sheva, Israel, PO Box 151
Principal Investigator: Itai Levi         
Rambam medical center hematology department Recruiting
Haifa, Israel, 4655202
Contact: Tsila Zuckerman, MD       'Tsila Zuckerman' <t_zuckerman@rambam.health.gov.il>   
Principal Investigator: Tsila Zuckerman, prof         
Shaare Zedek Medical Center Recruiting
Jerusalem, Israel, P.O.B 3235
Principal Investigator: Chezi Ganzel         
Rabin Medical Center Recruiting
Petach Tikva, Israel, 49100
Principal Investigator: Ofir Wolach         
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel, 6423906
Principal Investigator: Moshe Yakir         
Sponsors and Collaborators
BioSight Ltd.

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Responsible Party: BioSight Ltd.
ClinicalTrials.gov Identifier: NCT03435848     History of Changes
Other Study ID Numbers: BST002
First Posted: February 16, 2018    Key Record Dates
Last Update Posted: February 27, 2019
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioSight Ltd.:
Acute Myeloid Leukemia
Unfit for standard induction therapy
Cytarabine
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms