Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PHI 101 for the Treatment of AML

NCT04842370 | Unknown Phase 1

• 1 other identifier: PHI-101-001
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out the maximum tolerable dose and safety of PHI-101, novel FLT3 inhibitor in the treatment of relapsed or refractory AML for patients who have received standard therapy or cannot tolerate standard therapy, and/or for whom no standard therapy exists. There will be two parts to the study, which we will call Phase Ia and Phase Ib. Phase Ia is called the dose escalation. Approximately 20 to 24 patients are planned to be enrolled into Phase Ia. Phase 1a is conducted to determine the best dose and schedule of dosing of PHI-101 to be used in Phase 1b. There will be 5 different dose levels of PHI-101 given to patients in Phase Ia. Phase Ib is called the dose expansion. Approximately 14-34 patients (approximately 14-17 patients in each of the 2 cohorts planned) of each cohort are planned in Phase Ib based on study design. Phase Ib is also being conducted to assess anti-leukemia response, changes in transfusion requirements, and safety of PHI-101 at the dose level identified during Phase Ia.

Conditions

Relapsed or Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Safety assessed through adverse events to determine maximum tolerated dose

  Safety will be measured by AEs, vital signs, ECG, clinical laboratory tests, physical examination, ECOG performance.

  From screening to the last Safety Follow up Visit(Safety Follow-up visit occurs 30 days after from EOT)

• Tolerability assessed by dose compliance

  Tolerability will be measured by reviewing data of dose interruptions, reductions, and doses administered

  From screening to the last Safety Follow up Visit(Safety Follow-up visit occurs 30 days after from EOT)

Study Arms (1)

Dose escalation and expansion of PHI-101

EXPERIMENTAL

Drug: PHI-101

Interventions

PHI-101 DRUG

PHI-101, oral, once-daily administration, consisting of 28-days per 1 cycle

Dose escalation and expansion of PHI-101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Note: Subjects with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive hepatitis B core antibody test followed by a quantitative HBV DNA \< 9 log (80) IU/mL are eligible for the study. Subjects who are inactive carriers of HBV/HCV are eligible for the study.

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Pharos iBio Co., Ltd.: collaborator

Study Sites (1)

Seoul National University Cancer Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute

Interventions

PHI-101

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Sung-Soo Yoon, MD. PhD

  Seoul National University Hospital, Seoul National University College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sung-Soo Yoon, MD. PhD

CONTACT

82-2-2072-3079; ssysmc@snu.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2021
• First Posted: April 13, 2021
• Study Start: June 8, 2020
• Primary Completion: May 21, 2022
• Study Completion: May 21, 2022
• Last Updated: April 20, 2021

Record last verified: 2021-04

Locations

KR (1)