A Phase 2/3 Multicenter, Open-label, 3-arm, 2-stage Randomized Study of ASP2215 (Gilteritinib), Combination of ASP2215 Plus Azacitidine and Azacitidine Alone in the Treatment of Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation in Patients Not Eligible for Intensive Induction Chemotherapy

Phase 1

• Conditions: ewly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation in Patients Not Eligible for Intensive Induction Chemotherapy; MedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-001790-41-IT
• Lead Sponsor: ASTELLAS PHARMA GLOBAL DEVELOPMENT, INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-22
• Last Update Posted: 2 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1803

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: 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 = 75 years of age.
b. Subject 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) and/or requiring oxygen < 2 liters per minute
6. Subject must meet the following criteria as indicated on the clinical laboratory tests:
¿ Serum AST and ALT = 2.5 x institutional upper limit of normal (ULN)
¿ Serum total bilirubin = 1.5 x institutional ULN
¿ Serum potassium = institutional LLN
¿ Serum magnesium = institutional LLN
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 Contraception Requirements] starting at screening and continue through the study period, and for at least 120 days after the final study drug
administration.
12. Male subject must not donate sperm starting at screening and throughout the study period and for 120 days after the final study drug administration.
13. Subject agrees not to participate in another interventional study while on treatment.
Waivers to the inclusion criteria will NOT be allowed.
Are the trial subjects under 18? no
Number

Exclusion Criteria

1. Subject was diagnosed as 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) 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 radiation therapy within 4 weeks prior to the first study dose.
9. Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A.
10. Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P-gp with the exception of drugs that are considered absolutely essential for the care of the subject.
11. Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
12. Subject has congestive heart failure classified as New York Hearth Association Class IV.
13. Subject with mean Fridericia-corrected QT interval (QTcF) > 450 ms at screening based on central reading.
14. Subject with a history of Long QT Syndrome at screening.
15. Subject has known pulmonary disease 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.
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.
Waivers to the exclusion criteria will NOT be allowed.
Subjects who present with leukocytosis are required to achieve a myeloblast count < 50 x 10^9/L prior to initiating study treatment to reduce the risk of differentiation syndrome. The following cytoreduction guidelines can be used to achieve this myeloblast count.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified