Study to Assess the Efficacy and Safety of BST-236 as a Single Agent in Adults Unfit for Intensive Chemotherapy with Relapsed or Refractory Acute Myeloid Leukemia or Higher-Risk Myelodysplastic Syndromes
- Conditions
- Patients unfit for intensive chemotherapy with AML or HR MDS that failed or relapsed following first line therapyMedDRA version: 20.0Level: HLTClassification code 10028536Term: Myelodysplastic syndromesSystem Organ Class: 100000004851MedDRA version: 21.1Level: LLTClassification code 10081514Term: Acute myeloid leukemia refractorySystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-003400-13-FR
- Lead Sponsor
- Groupe Francophone des Myélodysplasies (GFM)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 40
1. Documented diagnosis of MDS, according to World Health Organization (WHO) classification and assessed as higher risk MDS, prior to first line HMA treatment, according to the Revised International Prognostic Scoring System (IPSS-R) (IPSS-R overall score = 4.5)
Or
2. 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
3. Adult =18 years of age
3. Failure/relapse following prior first-line AML or MDS treatment, defined as:
For MDS:
i.Relapse after initial complete or partial response or stable disease with HI, according to International Working Group (IWG) 2006 criteria following treatment with; azacitidine, decitabine.
ii.Failure to achieve complete or partial response or stable disease with HI according to International Working Group (IWG) 2006 criteria after at least 4 cycles of azacitidine or decitabine all within the last 1 year.
iii.MDS progression while on azacitidine/decitabine treatment irrespective of the number of cycles the patient has received.
For AML:
i.Relapse after initial CR/CRi/CRh following treatment with; azacitidine, decitabine, LDAC, venetoclax+HMA, or venetoclax+LDAC
ii.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 all within the last 1 year.
iii.AML progression while on HMA, LDAC, or venetoclax+ HMA or Venetoclax+ LDAC irrespective of the number of cycles the patient has received.
5. The participant is not able to receive an allogeneic bone marrow transplantation (BMT) at the time of study enrolment (BMT may be an option once the patient completed the study).
6. Not eligible for intensive chemotherapy.
a.Age =75 years
Or
b.Age =18 years with at least one of the following comorbidities:
i.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
ii.Other comorbidity that the Investigator judges as incompatible with intensive chemotherapy, which must be documented
7. Creatinine clearance (MDRD) equation or measured by 24 hours urine collection =45 mL/min
8. 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)
9. Total bilirubin =3 XULN unless due to Gilbert disease
10. performance status = 2
11. Women of reproductive potential must have a negative serum pregnancy test within 48 hours of the first day of any BST-236 treatment course
12. Women of reproductive potential must use two forms of effective birth control methods
13. 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
14. 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
15. Patient must be able to adhere to the study visit schedule and other protocol requirements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F
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 combinations of venetoclax with either HMA or LDAC
5. Previous allogeneic HSCT or solid organ transplantation
6.Participation in a previous clinical trial involving use of an investigational drug within 90 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 /?L 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. Known infection with Hepatitis B Virus (HBV) Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV)
17. In 12 leads ECG, QTc>480msec or history of QT prolongation or Torsades de pointes
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): For MDS patients: <br>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 <br>For AML patients:<br>CR Rate, defined as the proportion of patients who achieve a CR per the IWG 2006 Criteria<br>;Timepoint(s) of evaluation of this end point: End of BST-236 induction whether patients received one or two induction cycle(s)<br>;Main Objective: To assess the efficacy and safety of BST-236 in patients unfit for intensive chemotherapy with AML or HR MDS that failed or relapsed following first line therapy;Secondary Objective: 1. Time to CR, response duration, EFS, and overall survival<br>2. Safety and toxicity profile of BST-236 in this population<br>3. Duration of cytopenias , and time spent in hospitalization<br>4.Evaluate the prognostic impact of MRD for AML Patients<br>
- Secondary Outcome Measures
Name Time Method