Newly diagnosed Acute Myeloid Leukemia patients MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Pracinostat 60 mg
Product Code: SB939
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pracinostat
CAS Number: 929016-96-6
Current Sponsor code: SB939
Concentration unit: mg milli
Sponsors
Helsinn Healthcare SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patient = 18 years of age with newly diagnosed, histologically or cytologically confirmed, AML including de novo, secondary to antecedent hematologic disorders, or treatment-related disease with intermediate or unfavorable-risk cytogenetics 2. Unable to receive intensive chemotherapy regimens at enrollment, based on one of the following: I. Age = 75 years, or II. Age 40 kg/m2 g. Renal impairment defined as serum creatinine > 1.3 mg/dL (> 115 µmol/L) or creatinine clearance or equal than 20% blasts in bone marrow 4. Peripheral white blood cell (WBC) count 30,000/µL For cyto-reduction, hydroxyurea is allowed during screening and up to Cycle 1, Days 1-14, to reduce WBC count to < 30,000 µL prior to Day 1. After Cycle 1, Day 14, hydroxyurea is prohibited. 5. ECOG performance status = 2 6. Adequate organ function as evidenced by the following laboratory findings: a. Total bilirubin = 2 × upper limit of normal (ULN) or < 3 x ULN for patients with Gilbert-Meulengracht Syndrome b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 × ULN 7. Serum creatinine = 1.5 × ULN according to institutional standards or creatinine clearance = 50 mL/min 8. QT-interval corrected according to Fridericia’s formula (QTcF) = 450 ms on electrocardiogram (ECG) at Screening 9. Male patient who is surgically sterile, or male patient who is willing to agree with the true abstinence (refrain from heterosexual intercourse) or who uses barrier contraceptive measures during the entire study treatment period and for 3 months after the last administration of study drug, and agree to refrain from donating sperm during the entire study treatment period and for 3 month after the last administration of study drug 10. Female patient who is of childbearing potential willing to use a highly effective contraceptive measure while participating on study, OR willing to agree with the true abstinence from heterosexual intercourse during the entire study treatment period and for 3 months after the last administration of study drug 11. Female patient who is of childbearing potential must have a negative serum pregnancy test result within 1 week prior to starting study drugs. 12. Willing to provide voluntary written informed consent before performance of any study related
Exclusion criteria
Exclusion criteria: 1. Able to receive intensive induction chemotherapy 2. AML-associated inv(16)/t(16;16)/del(16q), t(15;17) (i.e. promyelocytic leukemia) with/without secondary aberrations; t(8;21) lacking del (9q) or lacking complex karyotypes 3. Presence of an active malignant disease within the last 12 months, with the exception of adequately treated cervical cancer in-situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]). Other malignancies may be considered after consultation with the Medical Monitor 4. Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the Investigator’s opinion, could compromise the patient’s safety or put the study outcomes at risk 5. Uncontrolled arrhythmias; any Class 3-4 cardiac diseases as defined by the New York Heart Association (NYHA) functional classification (Appendix E) 6. Evidence of AML central nervous system (CNS) involvement 7. Previous therapy for AML except for the following, which are allowed: a. Hydroxyurea for cytoreduction b. One course of hypomethylating agent therapy (i.e.; up to 7 doses of azacitidine or 3-5 days of decitabine) within 30 days prior to enrollment (Day 1) 8. Use of experimental drugs = 30 days prior to screening 9. Received any prior HDAC inhibitor therapy 10. Received prior treatment with a hypomethylating agent, except as allowed in Exclusion Criterion 7.b 11. Known hypersensitivity to any components of pracinostat, azacitidine, or mannitol 12. Human immunodeficiency virus (HIV) infection or an active and uncontrolled infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) 13. Gastrointestinal (GI) tract disease that causes an inability to take oral medication, malabsorption syndrome, or a requirement for IV alimentation; prior surgical procedures affecting absorption; or uncontrolled inflammatory GI disease (e.g., Crohn’s disease, ulcerative colitis) 14. Any disease(s), psychiatric condition, metabolic dysfunction, or findings from a physical examination or clinical laboratory test result that would cause reasonable suspicion of a disease or condition, that contraindicates the use of pracinostat and/or AZA, that may increase the risk associated with study participation, that may affect the interpretation of the results, or that would make the patient inappropriate for this study 15. Breast-feeding woman. 16. Current smokers (uUse of patches, chewing gums or vaping nicotine containing fluids is permitted). Patients who stopped smoking at least 8 days prior to first pracinostat dosing can be enrolled, provided they refrain from smoking during the whole study.) 17. Prohibited concomitant medications 18. Uncontrolled infections 19. Received more than 1 prior cycle of HMA or bone marrow transplant for any prior hematological disorder antecedent to AML.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show superiority in terms of overall survival of treatment with pracinostat versus placebo in patients treated with Azacitidine as background therapy;Secondary Objective: • To describe the efficacy of pracinostat evaluating additional efficacy variables • To assess the safety and tolerability • To evaluate the pharmacokinetics of pracinostat and its main metabolites • To assess the possible drug interaction of Pracinostat on the PK of Azacitidine • To perform a health-economic evaluation of treatment and control group;Primary end point(s): The primary efficacy endpoint is the overall survival measured as the time from randomization until death from any cause. ;Timepoint(s) of evaluation of this end point: End of the study as defined in the protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Morphologic Complete Remission rate 2 - Cytogenetic Complete Remission (CRc) rate 3 - Complete Remission without minimal residual disease (CRmMRD-) rate 4- Transfusion independence;Timepoint(s) of evaluation of this end point: End of the study as defined in the protocol | — |
Countries
Argentina, Australia, Austria, Brazil, Czech Republic, France, Germany, Hungary, Italy, Korea, Republic of, Peru, Poland, Romania, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactMedical Monitor
Clinipace s.r.o.
Outcome results
None listed