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Ponatinib combined with chemotherapy for treating acute lymphoblastic leukemia

Combination of Ponatinib Plus Chemotherapy As Frontline Treatment For Patients With BCR/ABL1-Like Acute Lymphoblastic Leukemia (BCR/ABL1-Like ALL)

Phase 2 Interventional Gruppo Italiano Malattie EMatologiche dell'Adulto · NCT05306301

This study is testing if adding Ponatinib to chemotherapy can help adults with a specific type of acute lymphoblastic leukemia feel better and improve their chances of recovery.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment32 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorGruppo Italiano Malattie EMatologiche dell'Adulto Academic / other
Drugs / interventionsponatinib, chemotherapy, Methotrexate, prednisone
Locations24 sites (Avellino, AV and 23 other locations)
Trial IDNCT05306301 on ClinicalTrials.gov

What this trial studies

This phase II interventional study aims to evaluate the effectiveness of Ponatinib in combination with a chemotherapy regimen for adult patients diagnosed with BCR/ABL1-like acute lymphoblastic leukemia (ALL). The study will enroll 32 newly diagnosed patients aged 18 to 65 years who have a specific genetic profile indicating a poor prognosis. Participants will undergo a steroid pre-treatment phase before receiving Ponatinib, and their response will be monitored for minimal residual disease (MRD) negativity at several intervals. The study seeks to improve treatment outcomes for this high-risk patient population by utilizing targeted therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 years with newly diagnosed BCR/ABL1-like acute lymphoblastic leukemia.

Not a fit: Patients with a WHO performance status greater than 2 or those with active hepatitis or significant liver dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for adults with BCR/ABL1-like acute lymphoblastic leukemia.

How similar studies have performed: While targeted therapies have shown promise in similar contexts, this specific combination of Ponatinib and chemotherapy in BCR/ABL1-like ALL is a novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Age 18-65 years.
* De novo Ph+-like ALL, as defined by the BCR/ABL1-like predictor (13).
* WHO score ≤2.
* Adequate liver function, as defined by the following criteria: total serum bilirubin ≤1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, alanine aminotransferase (ALT) ≤2.5 × ULN or ≤2.5 x ULN or leukemia related.
* Adequate pancreatic function as defined by serum lipase and amylase ≤1.5 × ULN or leukemia related.
* No history of dyslipidemia, thrombotic events or cardiac disease.
* For females of childbearing potential, a negative pregnancy test must be documented.
* Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment through 12 months after the end of treatment.
* Signed informed consent, according to ICH/EU/GCP and national regulation.

Exclusion Criteria:

* WHO performance status \>2.
* Active HBV or HCV hepatitis, or AST/ALT \> 2.5 x ULN and bilirubin \> 1.5 x ULN.
* History of acute pancreatitis within 1 year of study or history of chronic pancreatitis.
* History of alcohol abuse.
* Ongoing or active infections.
* Uncontrolled hypertriglyceridemia (triglycerides \>450 mg/dL).
* Clinically significant, uncontrolled or active cardiovascular disease, specifically including, but not restricted to:
* Any history of myocardial infarction, stroke, or revascularization, unstable angina or transient ischemic attack within 6 months prior to enrollment,
* Congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards,
* History of clinically significant (as determined by the treating physician) atrial arrhythmia,
* Any history of ventricular arrhythmia,
* Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism.
* Uncontrolled hypertension (diastolic blood pressure \>90 mm Hg; systolic \>140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
* Taking medications that are known to be associated with torsades de pointes.
* Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib.
* Creatinine levels \> 2.5mg/dl or glomerular filtration rate (GFR) \< 20 ml/min or proteinuria \>3.5 g/day.
* Gastrointestinal (GI) function impairment, or a GI disease that may significantly alter the absorption of study drugs.
* Patients who are currently receiving treatment with any of the medications with potential to prolong QT interval (listed in Appendix F) if the medications cannot be either discontinued or switched to a different medication prior to starting study drug.
* Patients who have received any investigational drug ≤ 4 weeks.
* Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
* Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs. prior to administration of Ponatinib). Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ two effective reliable methods of birth control throughout the study and for up to 12 months following discontinuation of study drugs.
* Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
* Patients unwilling or unable to comply with the protocol.

Where this trial is running

Avellino, AV and 23 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions ChemotherapyLeukemia, Acute Lymphoblastic
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.