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

  • STATUS
    Recruiting
  • End date
    Jul 31, 2027
  • participants needed
    230
  • sponsor
    Takeda
Updated on 7 October 2022
cancer
remission
imatinib
philadelphia chromosome
methotrexate
cytarabine
vincristine
ponatinib
prednisone
minimal residual disease
residual tumor
dexamethasone

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.

Description

The drug being tested in this study is called ponatinib. Ponatinib is being tested to treat people who have newly diagnosed Ph+ ALL. This study will look at the efficacy of ponatinib in participants in addition to standard care.

The study will enroll approximately 230 participants. Participants will be randomized in a 2:1 ratio to receive oral ponatinib or imatinib (Cohort A and Cohort B, respectively) daily throughout the study.

All participants will be asked to take ponatinib or imatinib at the same time each day with reduced-intensity chemotherapy in induction phase (Cycles 1 to 3), consolidation phase (Cycles 4 to 9) and maintenance phase (Cycles 10 to 20). At the end of the 20 cycles, participants will remain on ponatinib or imatinib (administered as a single agent). The dose of ponatinib in consolidation and maintenance phase will start with the last dose given in the previous phase. The dose can be modified based on MRD-negative CR results.

This multi-center trial will be conducted in Argentina, Australia, Austria, Belarus, Brazil, Bulgaria, Canada, Chile, France, Mexico, Greece, Italy, Japan, Korea, Republic Of, Poland, Romania, Russia, Spain, Taiwan, Province Of China, Turkey, Finland and the United States. Participants including those who achieve a clinical response, may receive study drug until they are deceased, have failed to achieve the primary endpoint, have experienced relapse from CR or have progressive disease, have an unacceptable toxicity, have withdrawn consent, have proceeded to HSCT, or until the sponsor terminates the study, whichever occurs first. After disease progression, all participants will be contacted every 3 months for survival follow-up. Participants will be followed until completion of the study or until the participant's death has been reported.

Details
Condition Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)
Treatment methotrexate, cytarabine, prednisone, Dexamethasone, vincristine, Imatinib, Ponatinib
Clinical Study IdentifierNCT03589326
SponsorTakeda
Last Modified on7 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Newly diagnosed Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL, as defined by the 2017 national comprehensive cancer network (NCCN) guidelines
Eastern Cooperative Oncology Group (ECOG) performance status of <=2

Exclusion Criteria

With a history or current diagnosis of chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML)
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
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)
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
Uncontrolled active serious infection 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 human immunodeficiency virus (HIV) seropositivity, known active hepatitis B or C infection
History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis
Uncontrolled hypertriglyceridemia (triglycerides >450 milligram per deciliter [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. Participants 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 venous thrombotic/embolic event (VTE) disease
Have a significant bleeding disorder unrelated to ALL
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