A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia
Condition: Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Philadelphia Chromosome
Intervention: Ponatinib; Imatinib; Vincristine; Dexamethasone; Cytarabine; Methotrexate; Prednisone
Intervention description: Ponatinib Tablets.; Imatinib Tablets.; Vincristine IV injection.; Dexamethasone Tablets.; Cytarabine IV infusion.; Methotrexate IV infusion.; Prednisone Tablets.
Intervention MeSH terms: Cytarabine; Dexamethasone; Prednisone; Methotrexate; Vincristine; Imatinib Mesylate; Ponatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: It is an open-label trial, therefore investigators and participants are unblinded.
Enrollment: 245.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ponatinib; Imatinib mesylate; Bcr-Abl Tyrosine Kinase; Bcr-abl fusion proteins; Iclusig; Gleevec

Summary:

      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.
    

Eligibility criteria:

        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.