EUCTR2014-001617-12-NL进行中（未招募）1 期
A Randomized, Open-label, Phase 2 Trial of Ponatinib in Patients with Resistant Chronic Phase Chronic Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses - OPTIC
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 450
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •All patients must meet all of the following inclusion criteria for study entry:
- •1. Have chronic phase CML and are resistant to at least two prior tyrosine kinase inhibitors.
- •a. The diagnosis of CML will be made using standard hematopathologic and cytogenetic criteria. Chronic phase CML will be defined by all of the following:
- •i < 15% blasts in bone marrow
- •ii < 30% blasts plus promyelocytes in bone marrow
- •iii < 20% basophils in peripheral blood
- •iv = 100 × 109/L platelets (= 100,000/mm3)
- •v No evidence of extramedullary disease except hepatosplenomegaly
- •vi No prior diagnosis of AP- or BP-CML
- •b. Cytogenetic assessment at screening must demonstrate the BCR-ABL fusion by presence of the t(9;22) Philadelphia chromosome.
- •i Variant translocations are only allowed provided they are assessable for cytogenetic response utilizing conventional cytogenetic techniques
- •ii Conventional chromosome banding must be performed
- •iii A minimum of 20 metaphases must be assessable at entry
- •c. Resistance to prior TKI therapy is defined as follows (patients must meet at least 1 criterion):
- •i Three months after the initiation of prior TKI therapy: No cytogenetic response (> 95% Ph+) or failure to achieve CHR or new mutation
- •ii Six months after the initiation of prior TKI therapy: BCR-ABLIS >10% and/or Ph+ >65% or new muation
- •iii Twelve months after the initiation of prior TKI therapy: BCR-ABLIS >10% and/or Ph+ >35% or new muation
- •iv At any time after the initiation of prior TKI therapy, the development of new BCR-ABL kinase domain mutations in the absence of CCyR or PCyR
- •v At any time after the initiation of prior TKI therapy, the development of new clonal evolution in the absence of CCyR or PCyR
- •vi At any time after the initiation of prior TKI therapy, the loss of of CHR, the loss of CCyR or PCyR, or the confirmed loss of MMR in 2 consecutive tests, one of which has a BCR-ABLIS transcript level of =1% or new mutation
- •2. Be male or female patients = 18 years old.
- •3. Have an ECOG performance status of 0, 1, or 2.
- •4. Have adequate renal function as defined by the following criterion:
- •a. Serum creatinine = 1.5 × ULN for institution
- •5. Have adequate hepatic function as defined by the following criteria:
- •a. Total serum bilirubin = 1.5 × ULN, unless due to Gilbert’s syndrome
- •b. ALT = 2.5 × ULN, or = 5 × ULN if leukemic involvement of the liver is present
- •c. AST = 2.5 × ULN, or = 5 × ULN if leukemic involvement of the liver is present
- •6. Have normal pancreatic status as defined by the following criterion:
- •a. Serum lipase and amylase = 1.5 × ULN
- •7. Have normal QT interval corrected (Frederica) (QTcF) interval on screening ECG evaluation, defined as QTcF of = 450 ms in males or = 470 ms in females.
- •8. Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
- •9. Agree to use a highly effective form of contraception with sexual partners from randomization through at least 4 months after the end of treatment (for female and male patients who are fertile).
- •10. Provide written informed consent.
- •11. Be willing and able to comply with scheduled visits and study procedures.
- •12. Have fully recovered (= grade 1, returned to baseline, or deemed irreversible) from the acute effects of prior cancer therapy before initiation of study drug.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 330
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of
排除标准
- •Patients are not eligible for participation in the study if they meet any of the following exclusion criteria:
- •1. Have used any approved TKIs or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is longer, prior to receiving study drug.
- •2. 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, or have not recovered (> grade 1 by NCI CTCAE, v4.0) from AEs (except alopecia), due to agents previously administered.
- •3. Have undergone autologous or allogeneic SCT < 60 days prior to receiving the first dose of ponatinib; have any evidence of ongoing GVHD or GVHD requiring immunosuppressive therapy.
- •4. Are being considered for HSCT within 6-12 months of enrollment (note: ponatinib is not to be used as a bridge to HSCT in this trial).
- •5. Are taking medications with a known risk of Torsades de Pointes
- •6. Have previously been treated with ponatinib.
- •7. Are in MCyR, defined as CCyR, PCyR, or MR2, which is =1% BCR-ABLIS.
- •8. Have active CNS disease as evidenced by cytology or pathology; in the absence of clinical CNS disease, lumbar puncture is not required. History itself of CNS involvement is not exclusionary if CNS has been cleared with a documented negative lumbar puncture.
- •9. Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
- •a. Any history of MI, unstable angina, cerebrovascular accident, or TIA
- •b. Any history of peripheral vascular infarction, including visceral infarction
- •c. Any revascularization procedure, including the placement of a stent
- •d. Congestive heart failure (CHF) (NYHA class III or IV) within 6 months prior to enrollment, or LVEF less than lower limit of normal, per local institutional standards, within 6 months prior to enrollment
- •e. History of clinically significant (as determined by the treating physician) atrial arrhythmia or any history of ventricular arrhythmia
- •f. Venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 6 months prior to enrollment
- •10. Have uncontrolled hypertension (diastolic blood pressure > 90 mmHg; systolic > 150 mmHg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
- •11. Have poorly controlled diabetes, defined as HbA1c values over the previous year of > 7.5% (59 mmol/mol) on more than 3 occasions; patients with preexisting, well-controlled, diabetes are not excluded.
- •12. Have a significant bleeding disorder unrelated to CML.
- •13. Have a history of alcohol abuse.
- •14. Have a history of either acute pancreatitis within 1 year of study or of chronic pancreatitis.
- •15. Have malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drug.
- •16. Have a history of another malignancy, other than cervical cancer in situ or nonmetastatic basal cell or squamous cell carcinoma of the skin; the exception is if patients have been
- •disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
- •17. Are pregnant or lactating.
- •18. Have undergone major surgery (with the exception of minor surgical procedures, such as catheter placement) within 14 days prior to first dose of ponatinib.
- •19. Have an ongoing or active infection; this includes, but is not limited to, the requirement for intravenous ant
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