Skip to main content

An Efficacy Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Participants With Newly Diagnosed Ph+ ALL

Trial Status: Active

The purpose of this study is to compare the efficacy of ponatinib versus imatinib, administered as first-line therapy in combination with reduced-intensity chemotherapy, in participants with newly diagnosed Ph+ ALL, as measured by the minimal residual disease (MRD)-negative complete remission (CR) at the end of induction.

Inclusion Criteria

  • Newly diagnosed Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL, as defined by the 2017 national comprehensive cancer network (NCCN) guidelines.
  • Molecular assessment of BCR-ABL1 must demonstrate the presence of a p190 (that is e1a2) or p210 (that is, e13a2 or e14a2 [also known as b2a2 or b3a2]) transcript type.
  • 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.
  • 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.

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: ACTIVE
Contact: Pankit Vachhani
Phone: 347-863-7340

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: APPROVED
Contact: Vladimir Kustanovich
Phone: 310-206-5756

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: ACTIVE
Contact: Bobbie Ann Frye
Phone: 317-274-2992

Kansas

Kansas City
University of Kansas Cancer Center
Status: IN_REVIEW
Contact: Marc Morrison
Phone: 913-588-7585

Maryland

Baltimore
University of Maryland / Greenebaum Cancer Center
Status: ACTIVE
Contact: Jennifer Pumphrey
Phone: 410-917-9346

New Jersey

Hackensack
Hackensack University Medical Center
Status: ACTIVE

New York

Buffalo
Roswell Park Cancer Institute
Status: ACTIVE

Oregon

Portland
OHSU Knight Cancer Institute
Status: ACTIVE

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE

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 230-320 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.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Millennium Pharmaceuticals, Inc.

  • Primary ID Ponatinib-3001
  • Secondary IDs NCI-2018-02292, 2018-000397-30, AP24534, U1111-1206-2370, HC6-24-c220300
  • Clinicaltrials.gov ID NCT03589326