A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)
About this trial
This is an interventional treatment trial for Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL) focused on measuring Ponatinib, Imatinib mesylate, Bcr-Abl Tyrosine Kinase, Bcr-abl fusion proteins, Iclusig, Gleevec
Eligibility Criteria
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.
Sites / Locations
- University of Alabama at BirminghamRecruiting
- City of Hope - DuarteRecruiting
- University of California Los AngelesRecruiting
- Augusta University Georgia Cancer CenterRecruiting
- Indiana UniversityRecruiting
- Indiana Blood & Marrow TransplantationRecruiting
- University of Kansas Medical Center Research InstituteRecruiting
- University of Maryland Medical CenterRecruiting
- Hackensack University Medical CenterRecruiting
- Roswell Park Cancer InstituteRecruiting
- Monter Cancer CenterRecruiting
- Stony Brook University Medical Center
- Oregon Health and Science UniversityRecruiting
- The University of Texas MD Anderson Cancer CenterRecruiting
- Methodist HospitalRecruiting
- Sanatorio AllendeRecruiting
- Hospital Privado Centro Medico de CordobaRecruiting
- Royal North Shore HospitalRecruiting
- Box Hill HospitalRecruiting
- Monash Medical CentreRecruiting
- Ordensklinikum Linz ElisabethinenRecruiting
- Hanusch Krankenhaus Wiener GebietskrankenkasseRecruiting
- Universitaetsklinik Fuer Innere Medizin IRecruiting
- Hospital Sao Rafael-Monte TaborRecruiting
- Hospital Erasto GaertnerRecruiting
- Hospital da CidadeRecruiting
- Hospital de Clinicas de Porto AlegreRecruiting
- Hemocentro Campinas UnicampRecruiting
- Fundacao Doutor Amaral CarvalhoRecruiting
- Hospital das Clinicas da Faculdade de Medicina da Riberao Preto da Universidade de Sao PauloRecruiting
- HEMORIO Instituto Estadual de HematologiaRecruiting
- Instituto do Cancer do Estado de Sao PauloRecruiting
- Fundacao Antonio Prudente - A.C.Camargo Cancer CenterRecruiting
- University Multiprofile Hospital for Active Treatment Saint Ivan RilskiRecruiting
- 855 West 12th AvenueRecruiting
- The Ottawa HospitalRecruiting
- Hopital Charles-LeMoyneRecruiting
- Hopital Maisonneuve-RosemontRecruiting
- Henan Cancer HospitalRecruiting
- The First Affiliated Hospital of Soochow University/Suzhou First People's HospitalRecruiting
- The First Hospital of Jilin UniversityRecruiting
- The First Affiliated Hospital, Zhejiang UniversityRecruiting
- Institute of Hematology & Blood Diseases Hospital of CAMS & PUMCRecruiting
- Helsingin ja Uudenmaan sairaanhoitopiiriRecruiting
- Centre Hospitalier de Versailles Hopital Andre MignotRecruiting
- Institut Universitaire du Cancer de Toulouse OncopoleRecruiting
- Center Hospitalier Universitaire d'AngersRecruiting
- Centre Hospitalier Lyon SudRecruiting
- Evaggelismos General HospitalRecruiting
- University General Hospital of Athens AttikonRecruiting
- University General Hospital of Patras Panagia I VoithiaRecruiting
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei TumoriRecruiting
- Azienda Policlinico San MartinoRecruiting
- Azienda Ospedaliera San Gerardo di MonzaRecruiting
- Arcispedale Santa Maria NuovaRecruiting
- Ospedale dell'AngeloRecruiting
- Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-MalpighiRecruiting
- Azienda Ospedaliera Vito FazziRecruiting
- Istituto Scientifico Universitario San RaffaeleRecruiting
- Azienda Ospedaliero-Universitaria di Modena PoliclinicoRecruiting
- Azienda Ospedaliera Ospedali Riuniti Villa Sofia-CervelloRecruiting
- Azienda USL della RomagnaRecruiting
- Centro di Ematologia Policlinico Umberto I Universita Sapienza di RomaRecruiting
- Fondazione Policlinico Universitario Agostino GemelliRecruiting
- National Cancer Center Hospital EastRecruiting
- Aiiku HospitalRecruiting
- Tokai University HospitalRecruiting
- Okayama University HospitalRecruiting
- Chiba Aoba Municipal HospitalRecruiting
- Fukushima Medical University HospitalRecruiting
- The Catholic University of Korea St. Vincent's HospitalRecruiting
- Kyungpook National University HospitalRecruiting
- Chonbuk National University HospitalRecruiting
- Inje University Haeundae Paik HospitalRecruiting
- Yeungnam University HospitalRecruiting
- Hospital Universitario Dr. Jose Eleuterio GonzalezRecruiting
- Uniwersytecki Szpital Kliniczny we WroclawiuRecruiting
- Szpital Uniwersytecki w KrakowieRecruiting
- Uniwersyteckie Centrum KliniczneRecruiting
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-MazursRecruiting
- City Clinical Hospital named after Vikentiy Vikentyevich Veresaev
- Sverdlovsk Regional Clinical Hospital #1
- National Research Center for Hematology, Dept. of Hematology/Oncology and BMT
- Almazov Federal North-West Medical Research Centre of Department of Health of Russian Federation
- Institut Catala d'Oncologia Badalona - Hospital Germans Trias i PujolRecruiting
- Hospital Universitari Vall d'HebronRecruiting
- Hospital Universitario de SalamancaRecruiting
- Hospital Universitari i Politecnic La Fe de ValenciaRecruiting
- Hualien Tzu Chi HospitalRecruiting
- China Medical University HospitalRecruiting
- National Cheng Kung University HospitalRecruiting
- Ankara Universitesi Tp Fakultesi
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Cohort A: Ponatinib 30 milligram (mg)
Cohort B: Imatinib 600 mg
Ponatinib 30 mg, tablets, orally, once daily (QD), with vincristine 1.4 mg/m^2 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 and Days 11 to 14 for up to 3 cycles (each cycle will be of 28-days) in induction phase followed by ponatinib last dose of induction phase tablets, orally, QD, with cytarabine, 1000 mg/m^2 every 12 hours as a 2-hour IV infusion (<60 yrs) and 250 mg/m^2 every 12 hours (>=60 yrs), IV on Days 1, 3, and 5 of Cycles 2, 4, and 6, (cytarabine dose will be reduced/ discontinued in case of impaired renal function) and methotrexate, 1000 mg/m^2 (<60 yrs) and 250 mg/m^2 (>=60 yrs), IV infusion, on Day 1 of cycles 1, 3, and 5 in consolidation phase followed by ponatinib last dose of consolidation phase, tablets, orally, QD, with vincristine 1.4 mg/m^2, 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.
Imatinib 600 mg,tablets, orally,QD,along with vincristine 1.4 mg/m^2 (max 2 mg),IV,on Days 1 and 14 and dexamethasone 40 mg (<60 yrs) and 20 mg (≥60 yrs),orally,once on Days 1 through 4 and Days 11 through 14 in each 28-day cycle up to 3 cycles in induction phase followed by imatinib 600 mg,tablets,orally,QD, along with cytarabine, 1000 mg/m^2 every 12 hours as a 2-hour-IV infusion (<60 yrs) and 250 mg/m^2 every 12 hours (≥60 yrs), IV on Days 1,3, and 5 of each 28-day even cycles (Cycles 2,4,and 6), (cytarabine dose reduced/discontinued for participant with impaired renal function) and methotrexate, 1000 mg/m^2 (<60 yrs) and 250 mg/m^2 (≥60 yrs),IV infusion, on Day 1 of each 28-day odd cycles (Cycle 1,3,and 5) in consolidation phase followed by imatinib 600 mg,tablets,orally,QD, along 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 through 5 in each 28-day cycle up to 11 cycles in maintenance phase.