PHI-101-001

• Willing and able to understand and sign an informed consent form (ICF) and to comply with all aspects of the protocol.
• Female or male subjects aged ≥18 years of age.
• The ECOG performance status ≤2.
• Life expectancy more than 3 months.
• Phase Ia (dose escalation part only): Subjects with relapsed and/or refractory AML which is diagnosed with World Health Organization (WHO) classification9 who have received standard therapy or are intolerant of standard therapy, and/or for whom no standard therapy exists.
• Phase Ib (dose expansion): Subjects with relapsed and/or refractory AML which is diagnosed with WHO classification and who have a FLT3 abnormality (i.e., FLT3-ITD and/or TKD mutation) as determined by accredited laboratory.
• Female subjects must be surgically sterile, or have a monogamous partner who is surgically sterile, or be of postmenopausal status (at least 2 years or serum follicle stimulating hormone >40 mIU/mL and estradiol <20 pg/mL or according to the postmenopausal range definition for the laboratory involved), or commit to use an effective form of birth control (Appendix 5) for the duration of the study and for 90 days following the last PHI-101 administration.
• Sexually active males must commit to use an effective form of birth control (Appendix 5) while taking the drug and for 30 days after stopping PHI-101. A condom is required to be used by vasectomized men in order to prevent delivery of the drug via seminal fluid.
• Subject having laboratory values defined as:
  Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) >40 mL/min.

Total bilirubin <1.5 × upper limit of normal (ULN), except for subjects with Gilbert’s syndrome who are excluded if total bilirubin >3.0 × ULN or direct bilirubin ≥1.5 × ULN.
Alanine aminotransferase (ALT) <2.5 × ULN, except for subjects that have leukemic involvement of the liver, who are excluded if ALT <5 × ULN.
Aspartate aminotransferase (AST) <2.5 × ULN, except for subjects that have leukemic involvement of the liver, who are excluded if AST <5 × ULN.

• Presence of overt leptomeningeal or active central nervous system involvement with AML.
• Subject has a diagnosis of acute promyelocytic leukemia (APL), French American British classification M3 or WHO classification of APL with t(15;17)(q22;q12), or BCR ABL positive leukemia (chronic myelogenous leukemia in blast crisis).
• Subject has favorable risk cytogenetics as categorized by the National Comprehensive Cancer Network Guidelines Version 2, 2014 for AML.
• Subject has had hematopoietic stem cell transplant and meets any of the following:
  Is within 2 months of transplant from Cycle 1 Day 1. Has clinically significant Graft-versus-host disease requiring treatment. Has ≥ Grade 2 persistent nonhematological toxicity related to the transplant. Donor lymphocytes infusion is not permitted ≤30 days prior to study registration or during the first cycle of treatment.
• Subject has disseminated intravascular coagulation abnormality.
• Impaired cardiac function or clinically significant cardiac disease, including any of the following:
  Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association Grade ≥2), left ventricular ejection fraction <50% as determined by multiple gated acquisition (MUGA) or echocardiogram, uncontrolled hypertension, or clinically significant arrhythmia.
  QT interval as corrected by the Fridericia method (QTcF) >450 ms ECG or congenital long QT syndrome at the Screening Visit.
  Subject with hypokalemia and hypomagnesemia at Screening (defined as values below lower limit of normal).
  Acute myocardial infarction or unstable angina pectoris <3 months prior to study entry.
• Subjects with interstitial pneumonia or history of drug-induced interstitial pneumonia/pneumonitis.
• A positive human immunodeficiency virus (HIV) antibody test.
• Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test, or active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test.

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