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Relapsed or Refractory Acute Myeloid LeukemiaPhase 1NCT04842370

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

A Phase 1 study testing PHI-101 in people with Relapsed or Refractory Acute Myeloid Leukemia, run by Seoul National University Hospital at 1 site in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PHI-101
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteSouth Korea
Study dates
8 Jun 2020to 21 May 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Chronic liver disease or chronic hepatitis (Child Pugh Class B or C hepatic impairment).
  • Any gastrointestinal disorders interfering with study drug absorption or subjects who are unable to swallow tablets or capsules.
  • Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
  • Subjects receiving systemic chronic steroid therapy or any immunosuppressive therapy (≥10 mg/day prednisone or equivalent). Topical, inhaled, nasal, and ophthalmic steroids are allowed.
  • Use of any live vaccines against infectious diseases within 28 days of initiation of study treatment.
  • Use of medications, herbal products, or foods known to be moderate or potent inhibitors of P glycoprotein (P gp) within the last 7 days prior to Day 1 or known to be moderate or potent inducers of P gp within the last 14 days prior to Day 1 (see Section 6.5).
  • Subjects with a history of stroke or having active neurological symptoms, with the exception of chronic conditions which in the opinion of the neurologist, Investigator, and the Sponsor, would not impact on ongoing neurologic assessments while on study treatment.
  • Active uncontrolled infection requiring systemic or antiviral antibiotic therapy.
  • Major surgery within 2 weeks of the first dose of study treatment (mediastinoscopy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery).
  • Radiotherapy within 3 weeks of the first dose of study drug, except for palliative radiotherapy to a limited-field, such as for the treatment of bone pain or a focally painful tumor mass.
  • Presence of CTCAE ≥ Grade 2 toxicity (except alopecia, peripheral neuropathy, and ototoxicity, which are excluded if ≥ CTCAE Grade 3) due to prior cancer therapy.
  • Prior treatment with cytotoxic agents (except hydroxyurea given for controlling hyperleukocytosis) within 2 weeks prior to study drug administration, or other experimental agents or noncytotoxic agents within 5 half-lives prior to study drug administration.
  • Note: Subjects in Phase Ia of this study can still take PHI-101 before entering Phase Ib of this study.
  • Any medical condition that would, in the Investigator's judgment, prevent the subject's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results.
  • Pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test.

Trial locations and contacts

1 site in 1 country.

Sung-Soo Yoon, MD. PhD contact

82-2-2072-3079

ssysmc@snu.ac.kr

South Korea1 site, 1 recruiting

  • Seoul National University Cancer Hospital

    Seoul

    Sung-Soo Yoon, MD. PhD, 82-2-2072-3079, ssysmc@snu.ac.kr

    Recruiting

Other trials in South Korea

About this study

Official title: A Prospective, Phase Ia/Ib, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the FLT3 Inhibitor, PHI 101, Alone in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML)

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.

Being tested
PHI-101
Medical subject headings
Recurrence, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PHI-101Drug

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

Study groups in NCT04842370
Study groupRoleWhat they receive
Dose escalation and expansion of PHI-101ExperimentalNot described
Receives: Drug: PHI-101

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. Tolerability assessed by dose compliance

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Apr 2021
  2. Study start8 Jun 2020
  3. Primary completion21 May 2022 (estimated)
  4. Study completion21 May 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04842370
Sponsor's protocol ID
PHI-101-001
Status last verified
Apr 2021
First submitted
8 Apr 2021
Last updated
20 Apr 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PHI-101 in people with Relapsed or Refractory Acute Myeloid Leukemia, run by Seoul National University Hospital at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 20 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Sung-Soo Yoon, MD. PhD (82-2-2072-3079, ssysmc@snu.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety assessed through adverse events to determine maximum tolerated dose (time frame: From screening to the last Safety Follow up Visit(Safety Follow-up visit occurs 30 days after from EOT)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04842370.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2021.

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