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

NCT04471064 | Unknown Phase 1

• 1 other identifier: HY-XY0206-Ⅰ-02
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.To evaluate the safety and tolerability of xy0206 as single drug in the treatment of relapsed / refractory AML;
2. 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. 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. 4.To evaluate the primary efficacy of xy0206 as single drug in the treatment of relapsed / refractory AML patients;
5. 5.To evaluate biomarkers of xy0206 as single drug treatment for relapsed / refractory AML subjects.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (26)

• Maximum tolerable dose

  The occurrence of Maximum tolerable dose.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Dose limiting toxicity

  The occurrence of Dose limiting toxicity.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Adverse event

  The occurrence rate of Adverse event.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Adverse drug reactions

  The occurrence rate of adverse drug reactions.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Serious adverse events

  The occurrence rate of Serious adverse events.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Blood routine

  Check whether the red blood cell system, white blood cell system and platelet system are normal

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Urine routine

  Urine routine examination includes urine color, transparency, pH, red blood cells, white blood cells, epithelial cells, tube type, protein, specific gravity and urine sugar.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Stool routine

  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.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Blood biochemistry

  The contents of various ions, sugars, lipids, proteins, enzymes, hormones and metabolites in blood were detected

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Serum amylase / lipase

  Evaluation of pancreatic function

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Coagulation function

  Four coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB) were evaluated.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• ECG

  Evaluation of QT interval

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Echocardiography

  To evaluate the electrophysiological condition of the heart

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Imaging examination

  Chest X-ray/CT

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Body temperature

  One of the vital signs.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Blood pressure

  Assess whether systolic blood pressure and diastolic blood pressure are normal

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Heart rate

  One of the vital signs.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Breathing

  Assess if breathing is normal

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Skin

  Assess if the skin is normal.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Head

  Head examination includes head, eyes, ears, nose, lips, etc.Assess if head is normal

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Neck

  Neck examination includes thyroid gland, lymph node, etc.Assess if neck is normal.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Chest

  Chest examination includes lung, cardiovascular, etc.Assess if chest is normal.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Abdomen

  Abdominal examination includes liver and spleen.Assess if abdomen is normal.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Limbs

  Assess if limbs is normal.

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Nerves

  Assess nerve function by communication

  from the start of the medication to the end of the study or 28 days after cessation of medication

• Back/spine

  Assess if back/spine is normal.

  from the start of the medication to the end of the study or 28 days after cessation of medication

Study Arms (7)

XY0206-12.5mg

EXPERIMENTAL

Drug:XY0206;Dosage form:Tablet;Dosage：12.5mg; multiple dose phase

Drug: XY0206

XY0206-25mg

EXPERIMENTAL

Drug:XY0206;Dosage form:Tablet;Dosage：25mg; multiple dose phase

Drug: XY0206

XY0206-50mg

EXPERIMENTAL

Drug:XY0206;Dosage form:Tablet;Dosage：50mg; multiple dose phase

Drug: XY0206

XY0206-100mg

EXPERIMENTAL

Drug:XY0206;Dosage form:Tablet;Dosage：100mg; multiple dose phase

Drug: XY0206

XY0206-150mg

EXPERIMENTAL

Drug:XY0206;Dosage form:Tablet;Dosage：150mg; multiple dose phase

Drug: XY0206

XY0206-200mg

EXPERIMENTAL

Drug:XY0206;Dosage form:Tablet;Dosage：200mg; multiple dose phase

Drug: XY0206

XY0206-250mg

EXPERIMENTAL

Drug:XY0206;Dosage form:Tablet;Dosage：250mg; multiple dose phase

Drug: XY0206

Interventions

XY0206 DRUG

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.

XY0206-100mg; XY0206-12.5mg; XY0206-150mg; XY0206-200mg; XY0206-250mg; XY0206-25mg; XY0206-50mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients cannot participate in this clinical study if they meet any of the following conditions:
• Known allergy to the study drug or any of its ingredients; has been treated with sunitinib malate, or allergy to sunitinib malate;
• BCR / ABL positive leukemia (chronic myeloid leukemia);
• The subjects had central nervous system leukemia;
• The subjects had secondary AML after chemotherapy for other tumors (except MDS);
• 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);
• 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;
• 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;

Sponsors & Collaborators

• Shijiazhuang Yiling Pharmaceutical Co. Ltd: lead
• Proswell Medical Corporation: collaborator

Study Sites (1)

Institute of Hematology, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300052, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Junyuan Qi, MD

  Institute of Hematology, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

wei Wang, master

CONTACT

086-0311-66703017; wangwei001@yiling.cn

Jianxiang Wang, MD

CONTACT

022-23909120; wangjx@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 14, 2020
• Study Start: September 15, 2020
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2024
• Last Updated: May 18, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)