An Efficacy Study Comparing Ponatinib Versus Imatinib, Administered in Combination with Reduced-Intensity Chemotherapy, in Participants with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
- Conditions
- ewly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)MedDRA version: 24.0Level: LLTClassification code: 10080018Term: Philadelphia positive acute lymphocytic leukemia Class: 10029104Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Registration Number
- CTIS2023-508463-71-00
- Lead Sponsor
- Takeda Development Center Americas Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 258
Male or female patients aged 18 years or older., Newly diagnosed Ph+ or BCR-ABL1 positive ALL, as defined by the 2017 National Comprehensive Cancer Network guidelines., Eastern Cooperative Oncology Group performance status of =2., Clinical laboratory values as follows, within 30 days before randomization: a) Total serum bilirubin =1.5× the upper limit of normal (ULN), unless due to Gilbert's syndrome. b) Alanine aminotransferase (ALT) or aspartate aminotransferase =2.5× the ULN. c) Serum creatinine =1.5× the ULN and estimated creatinine clearance = 30 mL/minute (Cockcroft-Gault formula). d) Serum lipase <1.5× the ULN., Normal QT interval corrected per Fridericia method (QTcF) on screening electrocardiogram, defined as QTcF of =450 ms in males or = 470 ms in females., 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 (such as any form of hormonal contraception, eg, birth control pills or hormonal intra-uterine device [IUD]) 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 a longer period per any local regulation, eg, 35 days for patients in France), OR d) Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (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.), 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 patient. (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.), 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., Willingness and ability to comply with scheduled visits and study procedures
Patients with a history or current diagnosis of chronic phase, accelerated phase, or blast phase chronic myeloid leukemia, Uncontrolled hypertriglyceridemia (tg >450 mg/dL), Diagnosed and treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection, 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, Clinical manifestations of CNS or extramedullary involvement with ALL other than lymphadenopathy or hepatosplenomegaly, Autoimmune disease with potential CNS involvement, Known significant neuropathy of Grade=2 severity, 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 min) e) Uncontrolled HTN (systolic blood pressure [BP] =150mmHg and/or diastolic BP =90mmHg). Patients with Stage 2 HTN (systolic BP = 140mmHg and/or diastolic BP =90 mmHg) should be under treatment at study entry per the current AHA guidelines to ensure BP control. Patients requiring 3 or more antihypertensive medications should have controlled HTN for the past 6 months. Isolated elevation(s) of systolic and/or diastolic BP during screening are not exclusionary f) Any history of myocardial infarction, unstable angina, coronary artery disease, cerebrovascular accident, ischemic stroke, or transient ischemic attack. Note: patients with any history of these events, whether considered clinically significant or not, are excluded g) History of congestive heart failure or left ventricular ejection fraction <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) Patients with documented significant pleural or pericardial effusions unless thought to be secondary to leukemia k) Any history of venous thromboembolism, including but not limited to deep venous thrombosis or pulmonary embolism within 6 months before randomization, Poorly controlled diabetes, defined as glycosylated hemoglobin values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded, Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing, Ongoing uncontrolled nausea or vomiting of any severity, Prior/current treatment with any systemic anticancer therapy and/or radiotherapy for ALL, with the exception of an optional prephase therapy or chemotherapy induction (no more than 1 cycle), which should be discussed with the sponsor's medical monitor/designee, Have a significant bleeding disorder unrelated to ALL, Life-threatening illness unrelated to cancer, such as severe CNS, pulmonary, renal, or hepatic disease unrelated to cancer, Female patient
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the efficacy of ponatinib versus imatinib, administered as first-line therapy in combination with reduced-intensity chemotherapy, in patients with newly diagnosed Ph+ ALL, as measured by the MRD-negative CR rate at the end of induction.;Secondary Objective: To compare EFS between the 2 cohorts;Primary end point(s): Primary efficacy endpoint: MRD-negative CR (BCR-ABL/ABL1 =0.01% and meeting criteria for CR)
- Secondary Outcome Measures
Name Time Method