計劃書編號Ponatinib-3001
試驗執行中
2019-08-09 - 2026-12-31
Phase III
召募中3
ICD-10C91
淋巴性白血病
一項比較 Ponatinib 與 Imatinib 併用減低劑量化學治療用於新診斷的費城染色體陽性急性淋巴球性白血病 (Ph+ ALL) 患者的第 3 期、隨機分配、開放標示、多中心試驗
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試驗申請者
保瑞爾生技股份有限公司
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試驗委託 / 贊助單位名稱
保瑞爾生技股份有限公司
-
臨床試驗規模
多國多中心
-
更新日期
2026/04/01
試驗主持人及試驗醫院
實際收案人數
0 召募中
實際收案人數
0 召募中
Audit
無
實際收案人數
0 召募中
Audit
無
適應症
Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
試驗目的
主要目標：針對新診斷的 Ph+ ALL 患者，以在誘導結束時的 MRD 陰性 CR 率進行估量，比較做為第一線療法併用減低劑量化療施用之 Ponatinib 與 Imatinib 的療效。
藥品名稱
錠劑
主成份
Ponatinib
劑型
Tablet
Tablet
Tablet
劑量
10
30
30
評估指標
主要療效評估指標：誘導期結束時的 MRD 陰性 CR (BCR-ABL/ABL1 ≤0.01% 且符合 CR 標準)
主要納入條件
*Inclusion Criteria:
1.Male or female patients aged 18 years or older.
2.Newly diagnosed Ph+ or BCR ABL1-positive ALL, as defined by the 2017 NCCN guidelines.
3.Molecular assessment of BCR-ABL1 must demonstrate the presence of a p190 (ie, e1a2) or p210 (ie, e13a2 or e14a2 [also known as b2a2 or b3a2]) transcript type.
4.Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
5.Clinical laboratory values as follows, within 30 days before randomization:
a)Total serum bilirubin ≤1.5× the upper limit of normal (ULN).
b)Alanine aminotransferase or aspartate aminotransferase (AST) ≤2.5× the ULN.
c)Serum creatinine ≤1.5× the ULN and estimated creatinine clearance (CrCl) ≥40 mL/minute (Cockcroft-Gault formula).
d)Serum lipase and amylase <1.5× the ULN.
6.Normal QT interval corrected per Fridericia method (QTcF) on screening electrocardiogram (ECG), defined as QTcF of ≤450 ms in males or ≤470 ms in females.
7.Female patients who:
a)Are postmenopausal for at least 1 year before the screening visit, OR
b)Are surgically sterile, OR
c)If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 1 month after the last dose of study drug, OR
d)Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
8.Male patients, even if surgically sterilized (ie, status postvasectomy), who:
a)Agree to practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR
b)Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
9.Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
10.Willingness and ability to comply with scheduled visits and study procedures.
*Exclusion Criteria:
1.Patients with a history or current diagnosis of chronic phase, accelerated phase, or blast phase CML.
2.Prior/current treatment with any systemic anticancer therapy (including but not limited to any TKI) and/or radiotherapy for cancer, with the exception of an optional prephase therapy, which should be discussed with the sponsor’s medical monitor/designee.
3.Treatment with any investigational products within 30 days before randomization or 6 half-lives of the agent, whichever is longer.
4.Currently taking drugs that are known to have a risk of causing prolonged QTc or torsades de pointes (TdP) (unless these can be changed to acceptable alternatives or discontinued) (Appendix E).
5.Taking any medications or herbal supplements that are known to be strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4 within at least 14 days before the first dose of study drug (Appendix F).
6.Active serious infection requiring antibiotics within 14 days before the first dose of study drug.
7.Major surgery within 28 days before randomization (minor surgical procedures such as catheter placement or BM biopsy are not exclusionary criteria).
8.Ongoing or active systemic infection, known seropositive HIV, known active hepatitis B or C infection.
9.History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis.
10.Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).
11.Patients with nonmelanoma skin cancer or carcinoma in situ of any type are excluded if they have not undergone complete resection.
12.History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis.
13.Active ALL in the CNS (confirmed by cerebrospinal fluid [CSF] analysis).
14.Autoimmune disease with potential CNS involvement.
15.Known significant neuropathy of Grade ≥2 severity.
16.Clinically significant, uncontrolled, or active cardiovascular, cerebrovascular, or peripheral vascular disease, or history of or active VTE disease, including, but not restricted to:
a)Complete left bundle branch block.
b)Right bundle branch block plus left anterior hemiblock, or bifascicular block.
c)History of or presence of clinically significant ventricular or atrial tachyarrhythmias.
d)Clinically significant resting bradycardia (<50 beats per minute).
e)Uncontrolled hypertension (HTN); systolic BP ≥150 mmHg and/or diastolic BP ≥90 mmHg). Patients with Stage 2 HTN (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg should be under treatment at study entry per the current American Heart Association guidelines to ensure BP control. Patients requiring 3 or more antihypertensive medications should have controlled HTN for the past 6 months.
f)Any history of myocardial infarction (MI), unstable angina, coronary artery disease (CAD), cerebrovascular accident (CVA), ischemic stroke, or transient ischemic attack (TIA).
g)History of congestive heart failure (CHF) (New York Heart Association class III or IV) or left ventricular ejection fraction (LVEF) <40%, within 6 months before randomization.
h)Symptomatic peripheral vascular disease or history of infarction, including visceral infarction.
i)History of any revascularization procedure, including the placement of a stent.
j)History of pleural or pericardial effusions.
k)Any history of venous thromboembolism, including but not limited to deep venous thrombosis (DVT) or pulmonary embolism within 6 months before randomization.
17.Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded.
18.Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing.
19.Ongoing uncontrolled nausea or vomiting of any severity.
20.Diarrhea of Grade >1, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) categorization.
21.History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.
22.Have a significant bleeding disorder unrelated to ALL.
23.Life-threatening illness unrelated to cancer, such as severe CNS, pulmonary, renal, or hepatic disease unrelated to cancer.
24.Female patients who are lactating or breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug is administered.
25.Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
26.Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
1.Male or female patients aged 18 years or older.
2.Newly diagnosed Ph+ or BCR ABL1-positive ALL, as defined by the 2017 NCCN guidelines.
3.Molecular assessment of BCR-ABL1 must demonstrate the presence of a p190 (ie, e1a2) or p210 (ie, e13a2 or e14a2 [also known as b2a2 or b3a2]) transcript type.
4.Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
5.Clinical laboratory values as follows, within 30 days before randomization:
a)Total serum bilirubin ≤1.5× the upper limit of normal (ULN).
b)Alanine aminotransferase or aspartate aminotransferase (AST) ≤2.5× the ULN.
c)Serum creatinine ≤1.5× the ULN and estimated creatinine clearance (CrCl) ≥40 mL/minute (Cockcroft-Gault formula).
d)Serum lipase and amylase <1.5× the ULN.
6.Normal QT interval corrected per Fridericia method (QTcF) on screening electrocardiogram (ECG), defined as QTcF of ≤450 ms in males or ≤470 ms in females.
7.Female patients who:
a)Are postmenopausal for at least 1 year before the screening visit, OR
b)Are surgically sterile, OR
c)If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 1 month after the last dose of study drug, OR
d)Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
8.Male patients, even if surgically sterilized (ie, status postvasectomy), who:
a)Agree to practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR
b)Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
9.Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
10.Willingness and ability to comply with scheduled visits and study procedures.
*Exclusion Criteria:
1.Patients with a history or current diagnosis of chronic phase, accelerated phase, or blast phase CML.
2.Prior/current treatment with any systemic anticancer therapy (including but not limited to any TKI) and/or radiotherapy for cancer, with the exception of an optional prephase therapy, which should be discussed with the sponsor’s medical monitor/designee.
3.Treatment with any investigational products within 30 days before randomization or 6 half-lives of the agent, whichever is longer.
4.Currently taking drugs that are known to have a risk of causing prolonged QTc or torsades de pointes (TdP) (unless these can be changed to acceptable alternatives or discontinued) (Appendix E).
5.Taking any medications or herbal supplements that are known to be strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4 within at least 14 days before the first dose of study drug (Appendix F).
6.Active serious infection requiring antibiotics within 14 days before the first dose of study drug.
7.Major surgery within 28 days before randomization (minor surgical procedures such as catheter placement or BM biopsy are not exclusionary criteria).
8.Ongoing or active systemic infection, known seropositive HIV, known active hepatitis B or C infection.
9.History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis.
10.Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).
11.Patients with nonmelanoma skin cancer or carcinoma in situ of any type are excluded if they have not undergone complete resection.
12.History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis.
13.Active ALL in the CNS (confirmed by cerebrospinal fluid [CSF] analysis).
14.Autoimmune disease with potential CNS involvement.
15.Known significant neuropathy of Grade ≥2 severity.
16.Clinically significant, uncontrolled, or active cardiovascular, cerebrovascular, or peripheral vascular disease, or history of or active VTE disease, including, but not restricted to:
a)Complete left bundle branch block.
b)Right bundle branch block plus left anterior hemiblock, or bifascicular block.
c)History of or presence of clinically significant ventricular or atrial tachyarrhythmias.
d)Clinically significant resting bradycardia (<50 beats per minute).
e)Uncontrolled hypertension (HTN); systolic BP ≥150 mmHg and/or diastolic BP ≥90 mmHg). Patients with Stage 2 HTN (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg should be under treatment at study entry per the current American Heart Association guidelines to ensure BP control. Patients requiring 3 or more antihypertensive medications should have controlled HTN for the past 6 months.
f)Any history of myocardial infarction (MI), unstable angina, coronary artery disease (CAD), cerebrovascular accident (CVA), ischemic stroke, or transient ischemic attack (TIA).
g)History of congestive heart failure (CHF) (New York Heart Association class III or IV) or left ventricular ejection fraction (LVEF) <40%, within 6 months before randomization.
h)Symptomatic peripheral vascular disease or history of infarction, including visceral infarction.
i)History of any revascularization procedure, including the placement of a stent.
j)History of pleural or pericardial effusions.
k)Any history of venous thromboembolism, including but not limited to deep venous thrombosis (DVT) or pulmonary embolism within 6 months before randomization.
17.Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded.
18.Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing.
19.Ongoing uncontrolled nausea or vomiting of any severity.
20.Diarrhea of Grade >1, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) categorization.
21.History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.
22.Have a significant bleeding disorder unrelated to ALL.
23.Life-threatening illness unrelated to cancer, such as severe CNS, pulmonary, renal, or hepatic disease unrelated to cancer.
24.Female patients who are lactating or breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug is administered.
25.Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
26.Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
試驗計畫預計收納受試者人數
-
台灣人數
10 人
-
全球人數
240 人
