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

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ClinicalTrials.gov Identifier: NCT03850574
Recruitment Status : Recruiting
First Posted : February 22, 2019
Last Update Posted : February 25, 2019
Sponsor:
Information provided by (Responsible Party):
Hanmi Pharmaceutical Company Limited

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: HM43239 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : February 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: HM43239
This 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.
Drug: HM43239
Daily (QD), continuous dosing




Primary Outcome Measures :
  1. 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) ]
  2. Area Under the Concentration-Time Curve (AUC) [ Time Frame: until Cycle 3 Day1 (each cycle is 28 days except for cycle 1 of dose escalation) ]
  3. Maximum Serum Concentration (Cmax) [ Time Frame: until Cycle 3 Day1 (each cycle is 28 days except for cycle 1 of dose escalation) ]
  4. Time to maximum concentration (Tmax) [ Time Frame: until Cycle 3 Day1 (each cycle is 28 days except for cycle 1 of dose escalation) ]
  5. Change of clinical response to HM43239 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Cumulative Incidence or Relapse [ Time Frame: From the date of achievement of a remission until the date of relapse, assessed up to 3 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03850574


Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Naval Daver, Dr    713-794-4392    NDaver@mdanderson.org   
Korea, Republic of
Seoul National University Hospital Not yet recruiting
Seoul, Korea, Republic of, 03080
Asan Medical Center Not yet recruiting
Seoul, Korea, Republic of, 05505
Samsung Medical Center Not yet recruiting
Seoul, Korea, Republic of, 06351
Sponsors and Collaborators
Hanmi Pharmaceutical Company Limited

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Responsible Party: Hanmi Pharmaceutical Company Limited
ClinicalTrials.gov Identifier: NCT03850574    
Other Study ID Numbers: HM-FLTI-101
First Posted: February 22, 2019    Key Record Dates
Last Update Posted: February 25, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms