A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia

• Status: Recruiting
• Trial end date: 2027-07-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Millennium Pharmaceuticals, Inc.; Takeda
• Treatments: BB 1101; Cytarabine; Dexamethasone; Dexamethasone acetate; Imatinib Mesylate; Methotrexate; Ponatinib; Prednisone; Vincristine

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.