Open Actively Recruiting

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

About

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.

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase II

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
18 Years
Maximum Age
N/A
  • 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
  • Adult ≥18 years of age
  • 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.
  • Not able to receive an allogeneic bone marrow transplantation (BMT) at the time of study enrolment.
  • Not eligible for intensive chemotherapy;
    • Age ≥75 years Or
    • Age ≥18 years with at least one of the following comorbidities:
    • Significant heart or lung comorbidities, as reflected by at least one of the following:
    • 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
    • Chronic stable angina or congestive heart failure controlled with medication
    • Other comorbidity or conditions that the Investigator judges as incompatible with intensive chemotherapy, which must be documented
    • ECOG=2
  • Creatinine clearance (estimated by the Modification of Diet in Renal Disease (MDRD) equation or measured by 24 hours urine collection) ≥45 mL/min
  • 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)
  • Total bilirubin ≤3 XULN unless due to Gilbert disease
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • 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
  • 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)
  • 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
  • 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
  • Patient must be able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

  • MDS or AML evolving from a pre-existing myeloproliferative neoplasm (MPN)
  • MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN
  • Acute promyelocytic leukemia
  • Previous treatment for AML or MDS with drugs other than HMA or LDAC or combinations of venetoclax with either HMA or LDAC
  • Previous allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation
  • 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
  • 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
  • Administration of HMA, LDAC, or venetoclax within 14 days prior to Study Day 1
  • Previous treatment with cytarabine at a dose higher than 20 mg/ m2/d
  • Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
  • 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
  • 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)
  • 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
  • History of allergic reactions attributed to compounds of similar chemical composition as BST-236 and/or cytarabine
  • Life expectancy shorter than 3 months attributed to any known medical condition other than AML/MDS
  • In 12 leads ECG, corrected QT interval (QTc)>480msec or history of QT prolongation or Torsades de pointes

Join this Trial

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Study Stats
Protocol No.
21-000818
Category
Hematology-Oncology
Oncology
Contact
Bruck Habtemariam
Location
  • UCLA Westwood
For Providers
NCT No.
NCT04749355
For detailed technical eligibility, visit ClinicalTrials.gov.