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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)
EU CTIS ID: 2023-508463-71-00
What this study is testing
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.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Male or female patients aged 18 years or older. • In Argentina, male or female patients 40 years and older. • In South Korea, male or female patients who are either: a) aged ≥18 through <65 years with comorbidities and/or poor functional status that, after discussion/agreement with the medical monitor/designee, are considered to make the patient unfit for any intensive therapy, or b) aged ≥65 years.
- 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.)
You likely can't join if
- 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
See the full eligibility criteria
Who can join
- Male or female patients aged 18 years or older. • In Argentina, male or female patients 40 years and older. • In South Korea, male or female patients who are either: a) aged ≥18 through <65 years with comorbidities and/or poor functional status that, after discussion/agreement with the medical monitor/designee, are considered to make the patient unfit for any intensive therapy, or b) aged ≥65 years.
- 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
What rules you out
- 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 patients who are lactating or breastfeeding or have a positive serum pregnancy test during the screening period or have a positive urine pregnancy test on D1 before the first dose of study drug is administered
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
- Admission or evidence of illicit drug or alcohol abuse
- Treatment with any investigational products within 30 days before randomization or 6 half-lives of the agent, whichever is longer
- Currently taking drugs that are known to have a risk of causing prolonged QTc or TDP (unless these can be changed to acceptable alternatives or discontinued)
- Taking any medications or herbal supplements that are known to be strong inhibitors or strong inducers of cyt P450 3A4 within at least 14 days before the first dose of study drug
- Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
- Major surgery within 28 days before randomization (minor surgical procedures such as catheter placement or BM biopsy are not exclusionary criteria)
- Known seropositive HIV, known active hepatitis B or C infection
- History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis
The study team makes the final eligibility decision.
Where it's taking place
- Russian Federation
- Brazil
- Japan
- Argentina
- Korea, Republic of
- Mexico
- Turkey
- United States
- Australia
- China
- Taiwan
- Canada
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Russian Federation; Brazil; Japan; Argentina; Korea, Republic of; Mexico and 6 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.