A Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FMS-like Tyrosine Kinase (FLT3) Mutated Acute Myeloid Leukemia (AML)
- Subject is considered an adult according to local regulation at the time of signing informed consent form (ICF).
- Subject has defined AML by the World Health Organization (WHO) criteria (2017) and fulfills one of the following:
- Refractory to at least 1 cycle of induction chemotherapy
- Relapsed after achieving remission with a prior therapy
- Subject is positive for FLT3 mutation in bone marrow or blood after completion of the subject's last interventional treatment.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening.
- Subject must meet the following criteria as indicated on the clinical laboratory tests:
- Serum Aspartate aminotransferase (AST) and Alanine Aminotransferease (ALT) ≤ 2.5 x upper limit of normal (ULN)
- Serum total bilirubin (TBL) ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
- Subject is suitable for oral administration of study drug.
- A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 180 days after the final study drug administration.
- Female subject must agree not to breastfeed starting at screening and throughout the study period, and for at least 180 days after the final study drug administration.
- Female subject must not donate ova starting at screening and throughout the study period, and for at least 180 days after the final study drug administration.
- A male subject must not donate sperm starting at screening and throughout the treatment period, and for at least 120 days after the final study drug administration.
- A male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period, and for at least 120 days after the final study drug administration.
- Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the treatment period, and for 120 days after the final study drug administration.
- Subject agrees not to participate in another investigational study while on treatment.
- Subject was diagnosed as acute promyelocytic leukemia.
- Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
- Subject has AML secondary to prior chemotherapy for other neoplasms (except for myelodysplastic syndrome).
- Subject has clinically active central nervous system leukemia.
- Subject has uncontrolled or significant cardiovascular disease, including:
- A myocardial infarction within 12 months
- Uncontrolled angina within 6 months
- History of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes) or any history of arrhythmia
- Uncontrolled hypertension
- Subject has baseline left ventricular ejection fraction that is ≥ 45%.
- Subject has mean triplicate Fridericia-corrected QT interval (QTcF) > 450 ms at Screening based on central reading.
- Subject has congenital or acquired Long QT Syndrome at screening.
- Subject has hypokalemia and/or hypomagnesemia at screening.
- Subject has been diagnosed with another malignancy that requires concurrent treatment or hepatic malignancy regardless of the need for treatment.
- Subject has clinically significant coagulation abnormality unless secondary to AML.
- Subject is receiving or plans to receive concomitant chemotherapy or immunotherapy.
- Subject has had major surgery within 4 weeks prior to the first study dose.
- Subject has radiation therapy within 4 weeks prior to the first study dose.
- Subject requires treatment with concomitant drugs that are strong inducers of Cytochrome P450 (CYP3A).
- Subject has known pulmonary disease with diffusion capacity of lung for carbon monoxide ≤ 65%, forced expiratory volume in the first second (FEV1) ≤ 65%, dyspnea at rest or requiring oxygen or any pleural neoplasm.
- Subject with systemic fungal, bacterial, viral or other uncontrolled infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. Subject needs to be off pressors and have negative blood cultures for 48 hours.
- Subject has not recovered from any prior therapy related toxicities.
- Subject is known to have human immunodeficiency virus infection.
- Subject has active hepatitis B or C or other active hepatic disorder.
- Subject has previously been treated with gilteritinib, quizartinib or crenolanib (will only apply to subjects enrolled in the phase 2 portion of the study).
- Subject has active clinically significant graft-versus-host disease (GVHD) or is on treatment with systemic corticosteroids for GVHD.
- Subject has relapsed after allogeneic hematopoietic stem cell transplant (HCST).
- Subject has an active autoimmune disorder that makes the subject unsuitable for study treatment or participation.
- Subject has any condition that makes the subject unsuitable for study participation.
This study will have 2 phases. Phase 1: The phase 1 portion of this study is to establish the recommended phase 2 dose (RP2D) of gilteritinib given in combination with atezolizumab. Phase 2: The phase 2 portion of the study will treat patients with gilteritinib and atezolizumab at the RP2D and will enroll in two stages. The first stage will evaluate the remission rate and if a minimum rate is achieved, a second stage of enrollment will continue.
Trial Phase Phase I/II
Trial Type Treatment
Astellas Pharma Global Development, Inc.
- Primary ID 2215-CL-1101
- Secondary IDs NCI-2018-02964
- Clinicaltrials.gov ID NCT03730012