Clinical Trials /

A Phase Ib Study of CT053PTSA in Relapsed / Refractory Acute Myeloid Leukemia (AML)

NCT03125876

Description:

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of CT053PTSA in Relapsed/refractory AML patients with FLT3 gene mutation.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase Ib Study of CT053PTSA in Relapsed / Refractory Acute Myeloid Leukemia (AML)
  • Official Title: A Phase Ib, Multi-center, Open, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Ningetinib (CT053PTSA) in Relapsed / Refractory Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: PCD-DCT053-16-002
  • NCT ID: NCT03125876

Conditions

  • Acute Myeloid Leukemia (AML)

Interventions

DrugSynonymsArms
CT053PTSANingetinibCT053PTSA

Purpose

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of CT053PTSA in Relapsed/refractory AML patients with FLT3 gene mutation.

Detailed Description

      It is a multi-center , open-label, dose escalation study conducted in 2 parts.
      Dose-escalation part: Subjects will receive oral CT053PTSA once daily repeatedly until
      disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days. At
      least 3 subjects will receive CT053PTSA at each dose (60, 80, 100mg) for determination of
      Maximum Tolerated Dose(MTD) and Dose Limiting Toxicity (DLT) Dose reduction of CT053PTSA will
      be considered if study drug-related toxicities are observed in a subject after Cycle 1.

      Expansion part:Expansion cohort might be set to further investigate the safety and efficacy
      of CT053PTSA at or lower MTD dose recommended by dose-escalation part.
    

Trial Arms

NameTypeDescriptionInterventions
CT053PTSAExperimental60mg-100mg
  • CT053PTSA

Eligibility Criteria

        Inclusion Criteria:

          1. study population

             a) documented acute myeloid leukemia according to World Health Organization(WHO)
             criteria(excluding acute promyelocytic leukemia), with Fms-like Tyrosine Kinase 3
             (FLT3) gene mutation,refractory/relapsed after common or enhanced chemotherapy c)
             Recovered from toxicity of previous treatment d) Eastern Cooperative Oncology Group
             (ECOG) performance status of 0-1 e) Life expectation ≥ 12 weeks

          2. Subjects must have adequate organ function and meeting all of the following laboratory
             review before enrollment a)blood routine examination: WBC≤2000/mm3 b)liver function:
             Alanine aminotransferase (ALT) and Aspartate transaminase (AST) ≤2.5×upper limit of
             normal(ULN); serum bilirubin ≤ 1.5 × ULN c)renal function: Serum creatinine ≤ 1.5×ULN,
             or the creatinine clearance (CrCl)≥ 60 mL / min calculated by the Cockcroft-Gault
             formula d) electrolyte: serum potassium≥3.0mmol/L; serum calcium≥2.0 mmol/L e)
             abnormal serum amylase without symptom≤1.5 × ULN; serum Lipase ≤1.5× ULN f)
             coagulation function:fibrinogen≥1.0g/L; activated partial thromboplastin time(
             APTT)≦ULN+10s; prothrombin time(PT)≤ULN+3s g) no obvious organ dysfunction 3)subjects
             must volunteer to provide evidence of effective diagnosis prior to entry or to accept
             bone marrow puncture or biopsy for diagnosis, and accept bone marrow puncture or
             biopsy after treatment to evaluate the efficacy 4) Sign the informed consent

        Exclusion Criteria:

        Subject meeting any of the following criteria will be excluded.

          1. treatment history

               1. chemotherapy, immunotherapy, radiotherapy, or major surgery within 4 weeks prior
                  to administration;

               2. nitrosourea and mitomycin chemotherapy within 6 weeks prior to the
                  administration;

               3. have taken live vaccines within 4 weeks prior to /or concurrent with the
                  administration;

               4. received FLT3 or Axl inhibitors within 6 weeks prior to the administration;

               5. have received a trial investigational product, or participated in other clinical
                  trials within 4 weeks prior to administration

          2. disease history and surgery history

             a) documented promyelocytic leukemia (t (15; 17) (q22; q11) and / or promyelocytic
             leukemia(PML)/retinoic acid receptor alpha (RARa) positivity found in the chromosome,
             variant acute promyelocytic leukemia) b) with myeloid sarcoma or invasion of central
             nervous system; c) high blood pressure and not well controlled by drug (blood pressure
             ≥ 140/90 mmHg). Note: Blood pressure before the first administration (mean blood
             pressure of two measures that 24 hours interval or above ) should be controlled within
             140/90 mmHg.

             d) Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) <50%; e)
             NCI CTCAE 4.03 ≥ 2 grade of arrhythmia, or corrected QT interval(QTc )> 450 ms ;
             patients with a history of torsion or congenital QT prolonged syndrome; f) any of the
             illness bellowed within 12 months prior to administration: myocardial infarction,
             severe or unstable angina, coronary artery bypass graft or peripheral artery bypass
             surgery, congestive heart failure, cerebrovascular events (including Transient
             ischemic attack); g) multiple factors that affect oral medication (eg, can not
             swallow, chronic diarrhea and intestinal obstruction, etc.); h)obvious tendency of
             gastrointestinal bleeding, including the following cases: local active ulcer lesion,
             and fecal occult blood test(≥++); melena or hematemesis within 2 months;
             gastrointestinal bleeding may occurs considered by investigator.

             i)history of immunodeficiency, other acquired or congenital immunodeficiency,history
             of organ transplantation; j) previous thyroid dysfunction,thyroid function can not be
             maintained at the normal range even have drug taken.

             k)Human immunodeficiency virus(HIV) positivity l) Hepatitis B surface antigen
             (HBsAg)positivity, and in the active phase(hepatitis B nucleic acid quantity≥ 1.00 ×
             103copies / ml); m) Hepatitis C antibody(Anti-HCV) positivity and in the active phase
             (hepatitis C nucleic acid quantity ≥1.00 × 102copies / ml) n) severe retinopathy or
             exfoliation judged by the Investigator; o) severe electrolyte imbalance judged by the
             investigator; p) active infectious disease judged by the investigator; q) other acute
             or chronic medical or psychological illnesses that are not suitable for clinical
             trials considered by the investigator or sponsor;

          3. Pregnant or lactating women or female and male with fertility plan. 4)the therapy
             and/or drug forbidden

               1. taking anticoagulant or vitamin K antagonist such as warfarin, heparin or other
                  similar drugs;

               2. taking other anti-leukemia drugs at the same time, including traditional Chinese
                  medicine (some Chinese medicine can not be used listed in Annex 4);

               3. taking drugs that will prolong QT interval(including Ia and III antiarrhythmic
                  drugs);

               4. patients who need oxygen therapy every day;

               5. long-term use of corticosteroids (local inhalation excluded);

        5)others

        a) history of Psychotropic drugs abuse and can not drop or the mentally disordered; b) be
        used to drink grapefruit juice or too much tea, coffee and / or caffeine-containing drink,
        can not stop during the trial(including Cycle 1 and subsequent treatment period) c) in the
        vegistrator's judgment, there is a serious accompany disease that jeopardizes patient's
        safety or interfere with the completion of the study.
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:day 1-28
Safety Issue:
Description:Safety and Tolerability assessed through adverse events to determine maximum tolerated dose

Secondary Outcome Measures

Measure:Maximum observed plasma concentration (Cmax)
Time Frame:On day 1,8,15,22,29
Safety Issue:
Description:to assess the pharmacokinetic profile in patients with AML
Measure:Time of maximum observed plasma concentration (Tmax)
Time Frame:On day 1,8,15,22,29
Safety Issue:
Description:to assess the pharmacokinetic profile in patients with AML
Measure:Area under the plasma concentration time curve
Time Frame:On day 1,8,15,22,29
Safety Issue:
Description:to assess the pharmacokinetic profile in patients with AML
Measure:Objective response rate (ORR)
Time Frame:Through study completion, an expected average of 1.5 year
Safety Issue:
Description:based on investigator review of radiographic images

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sunshine Lake Pharma Co., Ltd.

Last Updated