Clinical trial · Interventional
A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia
A Phase 3, Randomized, Open-label, Multicenter Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
In this study, adults with newly-diagnosed Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) will receive first-line therapy of ponatinib or imatinib. The main aim of this study is to compare the number of participants on each treatment that show no signs of disease. Participants will take tablets of either ponatinib or imatinib at the same time each day combined with reduced-intensity chemotherapy for up to 20 months. Then, they will continue with single-agent therapy (ponatinib or imatinib) until they meet the discontinuation criteria from the study.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL) | — | UNRESOLVED | — |
Interventions
Interventions (7)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Cytarabine | Drug | Cytarabine | ALIAS |
| Dexamethasone | Drug | Dexamethasone | ALIAS |
| Imatinib | Drug | Imatinib | ALIAS |
| Methotrexate | Drug | Methotrexate | ALIAS |
| Ponatinib | Drug | Ponatinib | ALIAS |
| Prednisone | Drug | Prednisone | ALIAS |
| Vincristine | Drug | Vincristine | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Cohort A: Ponatinib 30 milligram (mg)
- description
- Ponatinib 30 mg, tablets, orally, once daily (QD), with vincristine 1.4 mg/m\^2 (max 2 mg) intravenous (IV), on Days 1 and 14 and dexamethasone 40 mg (\<60 years \[yrs\]) and 20 mg (≥60 yrs), orally, once on Days 1 to 4, Days 11 to 14 for up to 3 cycles (each cycle=28 days) in induction phase (reduced dose of ponatinib 15 mg upon achievement of MRD-negative CR at end of induction) followed by ponatinib last induction phase dose with cytarabine, 1000 mg/m\^2 as 2-hour IV infusion (\<60 yrs) and 250 mg/m\^2 (≥60 yrs) every 12 hours, IV on Days 1, 3, 5 of Cycles 2,4,6 and methotrexate, 1000 mg/m\^2 (\<60 yrs) and 250 mg/m\^2 (≥60 yrs), IV infusion, on Day 1 of cycles 1, 3, 5 in consolidation phase followed by ponatinib last consolidation phase dose with vincristine 1.4 mg/m\^2 (max 2 mg), IV, on Day 1 and prednisone 200 mg (\<60 yrs), 100 mg (≥60-69 yrs) and 50 mg(≥70 yrs) on Days 1 to 5 for up to 11 cycles in maintenance phase up to data cut-off date: 12 August 2022.
- interventionNames
- Drug: Ponatinib
- Drug: Vincristine
- Drug: Dexamethasone
- Drug: Cytarabine
- Drug: Methotrexate
- Drug: Prednisone
- type
- ACTIVE_COMPARATOR
- label
- Cohort B: Imatinib 600 mg
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: 1. Newly diagnosed Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL, as defined by the 2017 national comprehensive cancer network (NCCN) guidelines. 2. Eastern Cooperative Oncology Group (ECOG) performance status of \<=2. Exclusion Criteria: 1. With a history or current diagnosis of chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML). 2. Prior/current treatment with any systemic anticancer therapy (including but not limited to any tyrosine kinase inhibitor \[TKI\]) 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. 3. Currently taking drugs that are known to have a risk of causing prolonged corrected QT (QTc) or torsades de pointes (TdP) (unless these can be changed to acceptable alternatives or discontinued). 4. 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. 5. Uncontrolled active serious infection that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. 6. Major surgery within 28 days before randomization (minor surgical procedures such as catheter placement or BM biopsy are not exclusionary criteria). 7. Known human immunodeficiency virus (HIV) seropositivity, known active hepatitis B or C infection. 8. History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis. 9. Uncontrolled hypertriglyceridemia (triglycerides \>450 milligram per deciliter \[mg/dL\]). 10. Diagnosed and treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 11. 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. 12. Clinical manifestations of CNS or extramedullary involvement with ALL other than lymphadenopathy or hepatosplenomegaly. 13. Autoimmune disease with potential CNS involvement. 14. Known significant neuropathy of Grade \>=2 severity. 15. Clinically significant, uncontrolled, or active cardiovascular, cerebrovascular, or peripheral vascular disease, or history of or active venous thrombotic/embolic event (VTE) disease. 16. Have a significant bleeding disorder unrelated to ALL.
References
Publications (3)
- DERIVEDAshaye A, Shi L, Aldoss I, Montesinos P, Vachhani P, Rocha V, Papayannidis C, Leonard JT, Baer MR, Ribera JM, McCloskey J, Wang J, Rane D, Guo S. Quality-Adjusted Time Without Symptoms of Disease or Toxicity (Q-TWiST) in Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Comparison of Ponatinib Versus Imatinib. Cancer Med. 2025 Apr;14(7):e70780. doi: 10.1002/cam4.70780. PMID 40165400
- DERIVEDHanley MJ, Larson TR, Diderichsen PM, Largajolli A, Hui K, Srimani J, Wang B, Vorog A, Gupta N. Population Pharmacokinetic and Exposure-Response Analyses for Ponatinib in the Phase 3 PhALLCON Study. Clin Transl Sci. 2025 Mar;18(3):e70175. doi: 10.1111/cts.70175. PMID 40025846
- DERIVEDJabbour E, Kantarjian HM, Aldoss I, Montesinos P, Leonard JT, Gomez-Almaguer D, Baer MR, Gambacorti-Passerini C, McCloskey J, Minami Y, Papayannidis C, Rocha V, Rousselot P, Vachhani P, Wang ES, Wang B, Hennessy M, Vorog A, Patel N, Yeh T, Ribera JM. Ponatinib vs Imatinib in Frontline Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2024 Jun 4;331(21):1814-1823. doi: 10.1001/jama.2024.4783. PMID 38722621