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A Study of XY0206 Tablets in Patients With Relapsed / Refractory Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04471064
Recruitment Status : Not yet recruiting
First Posted : July 14, 2020
Last Update Posted : July 14, 2020
Sponsor:
Collaborator:
Proswell Medical Corporation
Information provided by (Responsible Party):
Shijiazhuang Yiling Pharmaceutical Co. Ltd

Tracking Information
First Submitted Date  ICMJE July 1, 2020
First Posted Date  ICMJE July 14, 2020
Last Update Posted Date July 14, 2020
Estimated Study Start Date  ICMJE August 2020
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2020)
  • Maximum tolerable dose [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    The occurrence of Maximum tolerable dose.
  • Dose limiting toxicity [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    The occurrence of Dose limiting toxicity.
  • Adverse event [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    The occurrence rate of Adverse event.
  • Adverse drug reactions [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    The occurrence rate of adverse drug reactions.
  • Serious adverse events [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    The occurrence rate of Serious adverse events.
  • Blood routine [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Check whether the red blood cell system, white blood cell system and platelet system are normal
  • Urine routine [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Urine routine examination includes urine color, transparency, pH, red blood cells, white blood cells, epithelial cells, tube type, protein, specific gravity and urine sugar.
  • Stool routine [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Routine stool tests include the detection of red and white blood cells in feces, bacterial sensitivity test, occult blood test (OB) and inspection of eggs.
  • Blood biochemistry [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    The contents of various ions, sugars, lipids, proteins, enzymes, hormones and metabolites in blood were detected
  • Serum amylase / lipase [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Evaluation of pancreatic function
  • Coagulation function [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Four coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB) were evaluated.
  • ECG [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Evaluation of QT interval
  • Echocardiography [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    To evaluate the electrophysiological condition of the heart
  • Imaging examination [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Chest X-ray/CT
  • Body temperature [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    One of the vital signs.
  • Blood pressure [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Assess whether systolic blood pressure and diastolic blood pressure are normal
  • Heart rate [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    One of the vital signs.
  • Breathing [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Assess if breathing is normal
  • Skin [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Assess if the skin is normal.
  • Head [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Head examination includes head, eyes, ears, nose, lips, etc.Assess if head is normal
  • Neck [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Neck examination includes thyroid gland, lymph node, etc.Assess if neck is normal.
  • Chest [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Chest examination includes lung, cardiovascular, etc.Assess if chest is normal.
  • Abdomen [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Abdominal examination includes liver and spleen.Assess if abdomen is normal.
  • Limbs [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Assess if limbs is normal.
  • Nerves [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Assess nerve function by communication
  • Back/spine [ Time Frame: from the start of the medication to the end of the study or 28 days after cessation of medication ]
    Assess if back/spine is normal.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of XY0206 Tablets in Patients With Relapsed / Refractory Acute Myeloid Leukemia
Official Title  ICMJE A Multicenter, Open, Dose Increasing Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Primary Efficacy of xy0206 Tablets in Relapsed / Refractory Acute Myeloid Leukemia Subjects
Brief Summary
  1. To evaluate the safety and tolerability of xy0206 as single drug in the treatment of relapsed / refractory AML;
  2. Evaluate the dose limited toxicity (DLT) and maximum tolerable dose (MTD) of xy0206 as single drug in the treatment of relapsed / refractory AML subjects.
  3. To evaluate the pharmacokinetic (PK), pharmacokinetic (PD) characteristics and PK / PD correlation of xy0206 as single drug treatment in relapsed / refractory AML subjects;
  4. To evaluate the primary efficacy of xy0206 as single drug in the treatment of relapsed / refractory AML patients;
  5. To evaluate biomarkers of xy0206 as single drug treatment for relapsed / refractory AML subjects.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE Drug: XY0206
Dosage form:Tablet;Multiple dose phase:Take the medicine once a day,1 tablet at a time.4 weeks of continuous medication is one course of treatment. After the first course of treatment, the subjects can continue to receive the experimental drug treatment until they meet the withdrawal criteria. The duration and interval of treatment were determined according to the accumulated condition after multiple dose.
Study Arms  ICMJE
  • Experimental: XY0206-12.5mg
    Drug:XY0206;Dosage form:Tablet;Dosage:12.5mg; multiple dose phase
    Intervention: Drug: XY0206
  • Experimental: XY0206-25mg
    Drug:XY0206;Dosage form:Tablet;Dosage:25mg; multiple dose phase
    Intervention: Drug: XY0206
  • Experimental: XY0206-50mg
    Drug:XY0206;Dosage form:Tablet;Dosage:50mg; multiple dose phase
    Intervention: Drug: XY0206
  • Experimental: XY0206-100mg
    Drug:XY0206;Dosage form:Tablet;Dosage:100mg; multiple dose phase
    Intervention: Drug: XY0206
  • Experimental: XY0206-150mg
    Drug:XY0206;Dosage form:Tablet;Dosage:150mg; multiple dose phase
    Intervention: Drug: XY0206
  • Experimental: XY0206-200mg
    Drug:XY0206;Dosage form:Tablet;Dosage:200mg; multiple dose phase
    Intervention: Drug: XY0206
  • Experimental: XY0206-250mg
    Drug:XY0206;Dosage form:Tablet;Dosage:250mg; multiple dose phase
    Intervention: Drug: XY0206
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: July 9, 2020)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must meet all of the following criteria before entering the group:

    1. At least 18 years old; 2. Based on the World Health Organization (WHO) 2016 classification, the patients who were confirmed by the morphology of bone marrow cells and met the diagnosis criteria of relapsed / refractory AML (refer to the Chinese diagnosis and treatment guidelines for relapsed and refractory acute myeloid leukemia (2017 version)), the diagnosis criteria of relapsed AML: after CR, the peripheral blood once again showed leukemia cells or the original / immature cells in bone marrow were more than 5% (except the bone marrow after consolidated chemotherapy) The diagnosis standard of refractory AML: the primary refractory disease that has not been completely relieved after two courses of chemotherapy induced by standard regimen (including cytarabine and an anthracycline or anthraquinone drug); 3. ECOG physical fitness score is ≤ 2 points ; 4 Estimated survival time ≥ 12 weeks; 5 The organ function level of subjects must meet the following requirements:

    • Blood routine test: WBC ≤ 30 × 109 / L (it is allowed to take hydroxyurea until 3 days before administration of test drug to stabilize WBC);
    • Blood biochemistry: serum creatinine (Scr) ≤ 1.5 × ULN or creatinine clearance rate (Ccr) ≥ 60 ml / min (using Cockcroft -Gault formula); alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤ 2.5 × ULN (liver with leukemia cell infiltration ≤ 5 × ULN), total bilirubin (TBIL) ≤ 1.5 × ULN;
    • Electrolyte: the content of potassium, sodium, calcium and magnesium in the blood is within the normal value range of the laboratory (if the abnormal laboratory result judged by the researcher is of no clinical significance or can be controlled within the normal value range by drugs in the screening period, the subject can be included in the group);
    • Coagulation function: INR ≤ 1.5 × ULN, APTT < 10 seconds, PT < 3 seconds, FIB ≥ 1.5g/l (blood products or drugs are allowed to be corrected 3 days before administration of test drugs);
    • Friderica corrected QT value (QTC) for male ≤ 450 ms or female ≤ 470 MS;
    • LVEF≥ 50%;
    • Urinary protein < 2 + was detected in urine routine. If urinary protein ≥ 2 +, 24-hour urinary protein quantification is needed, and only when 24-hour urinary protein < 2g can be enrolled in the group; 6. The serum pregnancy test must be carried out within 28 days before receiving the first dose of study drug and the result must be negative. The women of childbearing age and the male subjects agree to adopt the routine and effective contraceptive measures during the whole study period and within 6 months after the treatment; 7. The subjects should be willing to provide effective diagnosis evidence before treatment or accept bone marrow puncture or biopsy for diagnosis, and accept bone marrow puncture or biopsy for efficacy evaluation after treatment; 8. Volunteer to participate in clinical research and sign informed consent in writing.

Exclusion Criteria:

  • Patients cannot participate in this clinical study if they meet any of the following conditions:

    1. Known allergy to the study drug or any of its ingredients; has been treated with sunitinib malate, or allergy to sunitinib malate;
    2. BCR / ABL positive leukemia (chronic myeloid leukemia);
    3. The subjects had central nervous system leukemia;
    4. The subjects had secondary AML after chemotherapy for other tumors (except MDS);
    5. At the same time, patients with other malignant tumors (except for those with cured stage IB or lower grade cervical cancer, non-invasive basal cell or squamous cell skin cancer, malignant melanoma with complete remission (CR) > 10 years, and other malignant tumors with complete remission (CR) > 5 years);
    6. Treatment before the trial:

      • Previous treatment with FLT3 inhibitor;
      • Patients who have received allogeneic hematopoietic stem cell transplantation before;
      • Received chemotherapy, biotherapy, targeted antitumor therapy within 28 days before starting to use the study drug, and radiotherapy within 14 days;
      • Drugs with significant effect on P450 metabolic enzyme pathway taken within 2 weeks before the screening period;
      • Have participated in other clinical studies and applied research drugs within 28 days before starting to use research drugs;
      • Major surgery or significant traumatic injury within 28 days prior to the first administration of the study treatment or maybe major surgery is needed during the study treatment period;
      • Concomitant drugs that may cause QTc prolongation or induce torsade de pointes (TdP) are required, in addition to antimicrobials used as standard therapy for the prevention or treatment of infection and other such drugs considered essential by the researchers;
    7. The toxic and side effects caused by previous treatment did not recover to CTCAE ≤ 1, except for hair loss and other tolerable events judged by the researchers;
    8. Combined diseases:

      • One or more HBsAg, HCV, anti HIV or anti Treponema pallidum specific antibodies are positive;
      • Clinically significant gastrointestinal abnormalities that may affect drug intake, transport or absorption (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, peptic ulcer, etc.), subjects with total gastrectomy, or patients with malabsorption syndrome;
      • Have a history of uncontrolled epilepsy, central nervous system disease or mental illness;
      • Hypertension with poor drug control (persistent systolic blood pressure ≥ 150 mmHg and / or diastolic blood pressure ≥ 100 mmHg despite antihypertensive treatment);
      • Poorly controlled diabetes mellitus (fasting blood glucose continues to be > 7.1mmol/L despite hypoglycemic treatment), or insulin-dependent diabetes mellitus (type I diabetes), or non insulin-dependent diabetes mellitus with small vessel disease, or pancreatic dysfunction;
      • In the 12 months before the first application, there were any of the following conditions: symptomatic congestive heart failure (New York Heart Association class II-IV), uncontrolled arrhythmia, angina pectoris, myocardial infarction, stroke (except lacunar infarction), coronary / peripheral artery bypass surgery, pulmonary embolism;
      • Long QT syndrome with congenital long QT interval syndrome or known family history;
      • There is a history of LVEF falling below 40%;
      • Uncontrolled active infections (bacteria, viruses, fungi, etc.);
      • Bleeding grade ≥ grade 3 ;
      • Have adrenal insufficiency;
      • The thyroid function was abnormal in the past, or could not be maintained in the normal range even under the condition of drug treatment;
      • Currently, there are serious unhealed wounds, ulcers or fractures;
      • Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN);
    9. For female subjects: currently in pregnancy or lactation;
    10. Any previous or current disease, treatment, or laboratory abnormality that may interfere with the results of the study, affect the subject's participation in the whole process of the study, or the subject is not suitable for the study in the opinion of the investigator.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: wei Wang, master 086-0311-66703017 wangwei001@yiling.cn
Contact: Jianxiang Wang, MD 022-23909120 wangjx@ihcams.ac.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04471064
Other Study ID Numbers  ICMJE HY-XY0206-Ⅰ-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Shijiazhuang Yiling Pharmaceutical Co. Ltd
Study Sponsor  ICMJE Shijiazhuang Yiling Pharmaceutical Co. Ltd
Collaborators  ICMJE Proswell Medical Corporation
Investigators  ICMJE
Principal Investigator: Junyuan Qi, MD Institute of Hematology, Chinese Academy of Medical Sciences
PRS Account Shijiazhuang Yiling Pharmaceutical Co. Ltd
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP