The Study for CML Who Failed Prior TKIs or With T315I Mutation or Ph+ ALL Who Failed Prior TKIs or With T315I Mutation

Korábbi kezelés

• Received TKI therapy within 7 days prior to receiving the first dose of Ponatinib, or have not recovered (> grade 2 by NCI CTCAE v5.0) from AEs (except alopecia) due to agents previously administered.
• Received other therapies (excluding hydroxyurea) as follows:
  • Received interferon, cytarabine, or immunotherapy within 14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of Ponatinib.
• Underwent autologous or allogeneic stem cell transplant < 60 days prior to receiving the first dose of Ponatinib;
• Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
• Have previously been treated with Ponatinib or its analogues (including drug substance).
• Underwent major surgery (with the exception of minor surgical procedures, such as catheter placement or BM biopsy) within 14 days prior to first dose of Ponatinib.
• Taken herbal preparations or related over-the-counter preparations containing Chinese herbal ingredients within 2 weeks prior to the first dose of Ponatinib.
• Received TKI therapy within 7 days prior to receiving the first dose of Ponatinib, or have not recovered (> grade 2 by NCI CTCAE v.5.0) from AEs (except alopecia) due to agents previously administered.
• Received other therapies (excluding hydroxyurea) as follows:
  • For AP-CML patients, received interferon, cytarabine, or immunotherapy within 14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of Ponatinib.
  • For BP-CML patients, received chemotherapy within 7 days prior to the first dose of Ponatinib. Otherwise, 2a applies.
  • For Ph+ ALL patients, received corticosteroids within 24 hours before the first dose of Ponatinib; otherwise, 2a applies.
• Underwent autologous or allogeneic stem cell transplant < 60 days prior to receiving the first dose of Ponatinib.
• Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
• Have previously been treated with Ponatinib or its analogues (including drug substance).

Más betegség

• Have active central nervous system (CNS) disease, as evidenced by cytology or pathology.
• Have significant, uncontrolled, or active heart/brain/peripheral vascular diseases
• Have a significant bleeding disorder unrelated to CML
• Have a history of pancreatitis or alcohol abuse
• Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of orally administered Ponatinib.
• Have been diagnosed with another primary malignancy within the past 3 years (except for non-melanoma skin cancer, cervical cancer in situ, or controlled prostate cancer, which are allowed within 3 years).
• Infectious diseases test showed anti-HIV (+) or anti-HCV (+) or HbsAg (+) or TP (+).
• Suffer from any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the safety of the study drug.
• Have hypertension (diastolic blood pressure ≥ 90 mmHg and/or systolic blood pressure ≥ 140 mm Hg).
• Have active central nervous system (CNS) disease as evidenced by cytology or pathology for AP-CML, BP-CML, or Ph+ ALL.
• Have significant, uncontrolled, or active cardiovascular disease.
• Have a significant bleeding disorder unrelated to CML or Ph+ ALL.

Laborértékek

• Take medications that are known to be associated with Torsades de Pointes or QT interval prolongation.
• Severely increased hypertriglyceridemia (triglycerides ≥ 5.6 mmol/L).
• Take medications that are known to be associated with Torsades de Pointes or QT interval prolongation.
• Patients with AP-CML, BP-CML, or Ph+ ALL are excluded if a baseline BM aspirate adequate for cell count and differential report is not available.

Egyéb

• For CP-CML patients：
• Patients with CP-CML are excluded if they are in CCyR.
• Are pregnant or lactating.
• Any subject who is not suitable for the study in the opinion of the investigator.
  • For AP/BP-CML and ALL patients：
• Patients with AP-CML, BP-CML, or Ph+ ALL are excluded if they are in MaHR.
• Other exclusions are the same with No.11-No.21 of CP-CML.

• For CP-CML patients：
• Patients with CP-CML
  • Patients must either meet criterion 2 or 3:
• Be previously treated with and resistant or intolerant to either Dasatinib or Nilotinib:
• Develop the T315I mutation after any TKI therapy;
• Must be ≥18 years old.
• Provide written informed consent.
• Eastern Cooperative Oncology Group performance status ≤ 2.
• Minimum life expectancy of 3 months or more.
• Adequate renal function
• Adequate hepatic function
• Normal pancreatic status
• Normal QTc interval on screening electrocardiogram (ECG) evaluation under resting state, defined as QTc of ≤ 450 ms in males or ≤ 470 ms in females.
  • For AP/BP-CML and ALL patients：
• Patients with AP-CML and BP-CML or Ph+ ALL
• Other inclusions are the same with No.2-No.11 of CP-CML patients