Clinical Trials /

Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM43239 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT03850574

Description:

This is a Phase 1/2, open-label, multi-center study to assess the efficacy, safety, tolerability, pharmacokinetics, including recommended phase 2 dose (RP2D) of HM43239 monotherapy in subjects with relapsed or treatment-refractory acute myeloid leukemia (AML).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dose Escalation and Expansion Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM43239 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
  • Official Title: A Phase 1/2 Open Label, Multicenter, Dose Escalation and Expansion Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM43239 in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: HM-FLTI-101
  • NCT ID: NCT03850574

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
HM43239HM43239

Purpose

This is a Phase 1/2, open-label, multi-center study to assess the efficacy, safety, tolerability, pharmacokinetics, including recommended phase 2 dose (RP2D) of HM43239 monotherapy in subjects with relapsed or treatment-refractory acute myeloid leukemia (AML).

Trial Arms

NameTypeDescriptionInterventions
HM43239ExperimentalThis phase 1/2 study consists of dose escalation and expansion. Dose escalation cohort is planned up to 10 dose levels. If subject in the dose escalation cohort at any dose level achieves clinical response then the dose level will continue to enroll.
  • HM43239

Eligibility Criteria

        Inclusion Criteria:

          -  Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written
             Informed Consent including privacy language as per national regulations (e.g., HIPAA
             Authorization for U.S. site) must be obtained from the subject or legally authorized
             representative prior to any study-related procedures (including withdrawal of
             prohibited medication, if applicable).

          -  Patient is ≥ 18 years of age (or country's legal age of majority if the legal age was
             > 18 years) at the time of obtaining informed consent.

          -  Patient is defined as morphologically documented primary or secondary AML by the World
             Health Organization (WHO) criteria (2016) and fulfills one of the following:

               1. Refractory to at least 1 cycle of prior therapy

               2. Relapsed after achieving remission with a prior therapy

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

          -  Patient's interval from prior treatment to time of study drug administration is at
             least 2 weeks for cytotoxic agents (except hydroxyurea given for controlling blast
             cells), or at least 5 half-lives for prior experimental agents or noncytotoxic agents,
             including immunosuppressive therapy post hematopoietic stem cell transplantation
             (HSCT).

          -  Patient must meet the following criteria as indicated on the clinical laboratory tests
             Φ

               1. Serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) ≤ 2.5×
                  institutional upper limit normal (ULN)

               2. Total serum bilirubin ≤ 1.5× institutional ULN

               3. Serum creatinine ≤ 1.5× institutional ULN or an estimated glomerular filtration
                  rate (eGFR) of > 60 ml/min as calculated by the Modification of Diet in Renal
                  Disease (MDRD) equation.

          -  Patient is suitable for oral administration of study drug and has minimum life
             expectancy (≥ 3 months)

          -  Female patient must be either:

          -  Of non-child bearing potential

               1. Post-menopausal (defined as at least 1 year without any menses) prior to
                  screening, or

               2. Documented surgically sterile or status post hysterectomy (at least 1 month prior
                  to screening)

          -  Or, if of childbearing potential,

               1. Must have a negative serum or urine pregnancy test at screening Φ , and

               2. Must use two forms of birth control£ (at least one of which must be a barrier
                  method) starting at screening and throughout the study period and for 90 days
                  after the final study drug administration.

          -  Female patient must not be breastfeeding at screening and during the study period, and
             for 90 days after the final study drug administration

          -  Female patient must not donate ova starting at screening and throughout the study
             period, and for 90 days after the final study drug administration.

          -  Male patient and their female spouse/partners who are of childbearing potential must
             be using highly effective contraception consisting of two forms of birth control£ (one
             of which must be a barrier method) starting at screening and continue throughout the
             study period and for 90 days after the final study drug administration.

          -  Male patient must not donate sperm starting at screening and throughout the study
             period and for 90 days after the final study drug administration.

          -  Patient agrees not to participate in another interventional study while on treatment

        Exclusion Criteria:

        Patients must not enter the study if any of the following exclusion criteria are fulfilled.

          -  Patient was diagnosed as acute promyelocytic leukemia (APL)

          -  Patient has BCR-ABL-positive leukemia

          -  Patient has active malignant tumors other than AML, or Myelodysplastic Syndrome (MDS).

          -  Patient has persistent non-hematological toxicities of ≥ Grade 2 (CTCAE v4.03), with
             symptoms and objective findings, from prior AML treatment (including chemotherapy,
             kinase inhibitors, immunotherapy, experimental agents, radiation, or surgery)

          -  Patient has had hematopoietic stem cell transplant (HSCT) and meets any of the
             following:

               1. Has undergone HSCT within the 2 month period prior to the first study dose

               2. Has clinically significant graft-versus-host-disease(GVHD) requiring treatment

               3. Has ≥ Grade 2 persistent non-hematological toxicity related to the transplant
                  Donor lymphocytes infusion (DLI) is not permitted ≤ 30 days prior to the first
                  study dose or during the first two cycle of treatment on the study in Part A and
                  Part B

          -  Patient with symptomatic central nervous system (CNS) involvement of leukemia or other
             CNS diseases related to underlying and secondary effects of malignancy.

          -  Patient has disseminated intravascular coagulation abnormality (DIC) Φ.

          -  Patient has had major surgery within 4 weeks prior to the first study dose.

          -  Patient has had radiation therapy within 4 weeks prior to the first study dose.

          -  Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4,
             or patient with a history of congestive heart failure NYHA class 3 or 4 in the past,
             unless a screening echocardiogram or multigated acquisition (MUGA) scan performed
             within 3 months prior to study entry results in a left ventricular ejection fraction
             (LVEF) that is ≥ 45% Φ.

          -  Any of the following cardiac abnormalities of history

               1. Patient has any clinically important abnormalities in rhythm, conduction or
                  morphology of resting ECG, e.g., complete left bundle branch block, third-degree
                  heart block, second-degree heart block, or PR interval > 250milliseconds (ms).

               2. Patient has a mean QT interval (QTc) by Friderica's method (QTcF) > 450ms in
                  three successive Screening measurements.

               3. Patient has any factors that increase the risk of QTc prolongation or risk of
                  arrhythmic events, such as congenital long QT, syndrome, family history of long
                  QT syndrome.

               4. Patient is unable or unwilling to discontinue concomitant use of drugs that are
                  known to prolong the QT interval.

          -  Patient with an active infection. Φ

          -  Patient is known to have human immunodeficiency virus infection.

          -  Patient has known active hepatitis B or C, or other active hepatic disorder Φ.

          -  Patient has any condition which, in the investigator's opinion, makes the patient
             unsuitable for study participation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Number of patient with dose limiting toxicity (DLT)
Time Frame:During Cycle 1 (30 days in dose escalation part and 28 days in expansion part)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Best Response Rate per modified International Working Group criteria
Time Frame:Scr, Cycle2Day1 and Cycle3Day1. In case of showing clinical response, assessment will be repeated on 1 month after the date of remission and every 3 subsequent cycles (each cycle is 28 days except for cycle1 of dose escalation) until disease progression
Safety Issue:
Description:
Measure:Duration of Response
Time Frame:Time from the initial complete or partial response to the time of disease progression or death, assessed up to 3 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:From the date of entry into a clinical trial to the date of death from any cause, assessed up to 3 years
Safety Issue:
Description:
Measure:Event Free Survival
Time Frame:From the date of entry into a study to the date of primary refractory disease, or relapse from Complete Remission, or death from any cause, whichever occurs first, assessed up to 3 years
Safety Issue:
Description:
Measure:Cumulative Incidence or Relapse
Time Frame:From the date of achievement of a remission until the date of relapse, assessed up to 3 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hanmi Pharmaceutical Company Limited

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