Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation in Patients Not Eligible for Intensive Induction Chemotherapy MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Gilteritinib
Product Code: ASP2215
Pharmaceutical Form: Tablet
INN or Proposed INN: GILTERITINIB
Current Sponsor code: ASP2215
Concentration unit: mg milligram(s)
Concentration type: equ
Sponsors
Astellas Pharma Global Development, Inc. (APGD)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Institutional Review Board-/Independent Ethics Committee- (IRB/IEC)-approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] Authorization for United States [US] sites) must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Subject is considered an adult according to local regulation at the time of obtaining informed consent. 3. Subject has a diagnosis of previously-untreated AML according to World Health Organization (WHO) classification [Swerdlow et al, 2008] as determined by pathology review at the treating institution. 4. Subject is positive for FLT3 mutation (ITD or TKD [D835/I836] mutation) in bone marrow or whole blood as determined by central laboratory. NOTE: Requirement of FLT3 mutation assessment by central laboratory is only applicable to the randomization portion of the study. 5. Subject is ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria: a. Subject is = 65 years of age and ineligible for intensive induction chemotherapy per investigator’s discretion. b. Subject is = 18 to 64 years of age and has any of the following comorbidities: i. Congestive heart failure (New York Heart Association (NYHA) class = 3 ) or ejection fraction (EF) = 50%; ii. Creatinine > 2 mg/dL (177 µmol/L), dialysis or prior renal transplant; iii. ECOG performance status = 2; iv. Prior or current malignancy that does not require concurrent treatment; v. Subject has received a cumulative anthracycline dose above 400 mg/m2 of doxorubicin (or cumulative maximum dose of other another anthracycline) vi. Known pulmonary disease with decreased diffusion capacity of lung for carbon monoxide (DLCO > 50%) and/or requiring oxygen = 2 liters per minute vii. Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor during screening and before randomization. 6. Subject must meet the following criteria as indicated on the clinical laboratory tests: ? Serum AST and ALT = 3.0 x institutional upper limit of normal (ULN) ? Serum total bilirubin = 1.5 x institutional ULN ? Serum potassium = institutional LLN ? Serum magnesium = institutional LLN Repletion of potassium and magnesium levels during the screening period is allowed. 7. Subject is suitable for oral administration of study drug. 8. A female subject is eligible to participate if she is not pregnant and at least one of the following condictions applies: a) Not a woman of childbearing potential (WOCBP) as defined in [Appendix 12.1 Contraception Requirements] OR b) WOCBP agrees to follow the contraceptive guidance as defined in [Appendix 12.1 Contraception Requirements] starting at screening and continue through the study period, and for at least 180 days after the final study drug administration. 9. Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 60 days after the final study drug administration. 10. Female subject must not donate ova starting at screening and throughout the study period, and for 180 days after the final study drug administration. 11. A male subject with female partner(s) of childbearing potential must agree to use contraception as detailed in [Appendix 12.1 Contracep
Exclusion criteria
Exclusion criteria: 1. Subject was diagnosed with acute promyelocytic leukemia (APL). 2. Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis). 3. Subject has received previous therapy for AML, with the exception of the following: ? Emergency leukapheresis ? Hydroxyurea ? Preemptive treatment with retinoic acid prior to exclusion of APL = 7 days ? Growth factor or cytokine support ? Steroids 4. Subject has clinically active central nervous system leukemia. 5. Subject has been diagnosed with another malignancy that requires concurrent treatment (with the exception of hormone therapy limited to those therapies that prevent recurrence and/or spread of cancer) or hepatic malignancy regardless of need for treatment. 6. Subject has clinically significant coagulation abnormality unless secondary to AML in the opinion of the investigator. 7. Subject has had major surgery within 4 weeks prior to the first study dose. 8. Subject has had radiation therapy within 4 weeks prior to the first study dose. 9. Subject requires treatment with concomitant drugs that are strong inducers of CYP3A/P-gp. 12. Subject has congestive heart failure classified as New York Hearth Association Class IV. 13. Subject with mean Fridericia-corrected QT interval (QTcF) > 480 ms at screening based on central reading. 14. Subject with a history of Long QT Syndrome at screening. 15. Subject has known pulmonary function test with DLCO = 50%, forced expiratory volume in the first second (FEV1) = 60%, dyspnea at rest or any pleural neoplasm. (Transient use of supplemental oxygen is allowed.) 16. Subject has an active uncontrolled infection. If an infection is present, the patient must be receiving definitive therapy and have no signs of progressing infection. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. 17. Subject is known to have human immunodeficiency virus infection. 18. Subject has active hepatitis B or C or other active hepatic disorder ? Subjects with positive hepatitis B surface antigen (HBsAg) or detectable hepatitis B DNA are not eligible. ? Subjects with negative HBsAg, positive hepatitis B core antibody and negative hepatitis B surface antibody will be eligible if hepatitis B DNA is undetectable. ? Subjects with antibodies to hepatitis C virus will be eligible if hepatitis C RNA is undetectable. 19. Subject has any condition which, in the investigator’s opinion, makes the subject unsuitable for study participation, including any contraindications of azacitidine listed in the country package insert. 20. Subject has a known or suspected hypersensitivity to ASP2215, azacitidine or any components of the formulations used.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the efficacy superiority of ASP2215 plus azacitidine versus azacitidine as measured by overall survival (OS).;Secondary Objective: Determine the efficacy superiority of ASP2215 plus azacitidine versus azacitidine as measured by event-free survival (EFS). The additional secondary objectives are to: Evaluate the safety and efficacy of ASP2215 plus azacitidine versus azacitidine in terms of: • Best Response • Complete remission (CR) rate • CRc rate • CRh rate • CR/CRh rate • Transfusion conversion rate; transfusion maintenance rate • Leukemia-free survival (LFS) • Duration of remission • Patient-reported fatigue (Brief Fatigue Inventory [BFI]) • Adverse events (AEs), clinical laboratory results, physical examinations, vital signs, ECGs, and Eastern Cooperative Oncology Group (ECOG) performance scores ;Primary end point(s): - Overall Survival;Timepoint(s) of evaluation of this end point: up to 77 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoint: - Event-free survival Secondary Efficacy Endpoints: - Best Response - CR, CRc, CRh, CR/CRh - Transfusion conversion rate; transfusion maintenance rate - Leukemia-free survival - Duration of remission - Patient reported fatigue from BFI Safety Endpoints:AEs - AEs - Clinical laboratory results - Physical examinations - Vital sign measurements - ECGs - ECOG performance scores ;Timepoint(s) of evaluation of this end point: Up to 77 months | — |
Countries
Australia, Belgium, Brazil, Canada, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Malaysia, Poland, Russian Federation, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Unit
Astellas Pharma Europe B.V.
Outcome results
None listed