Active, not recruiting
Phase 3
A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia
Condition(s) studied
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)
Investigational drug(s) / intervention(s)
PonatinibImatinibVincristineDexamethasoneCytarabineMethotrexatePrednisone
Ponatinib: Ponatinib Tablets.
Imatinib: Imatinib Tablets.
Vincristine: Vincristine IV injection.
Dexamethasone: Dexamethasone Tablets.
Cytarabine: Cytarabine IV infusion.
Methotrexate: Methotrexate IV infusion.
Prednisone: Prednisone Tablets.
Study 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
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.
Primary outcome measure(s)
- Number of Participants With Minimal Residual Disease (MRD)-Negative Complete Remission (CR) at The End of Induction Phase — From Cycle 1 through Cycle 3 (approximately 3 months) (Cycle length = 28 days)
MRD-negative CR was achieved when a participant met the criteria for both MRD negativity and CR. MRD-negativity: ≤0.01 % breakpoint cluster region-Abelson (BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in complementary deoxyribonucleic acid (cDNA) with ≥ 10,000 ABL1 transcripts. CR: meeting all the following for at least 4 weeks (that is no recurrence):1. No circulating blasts and less than (\<) 5% blasts in the bone marrow (BM). 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (central nervous system \[CNS\] involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. Absolute neutrophil count (ANC) \> 1000 per microliter (/mcL) (or \>1.0\*10\^9/L). 5. Platelets \>100,000/mcL (or \>100\*10\^9/L).
Trial sites (92)
| Facility | City | Region | Status |
| University of Alabama at Birmingham |
Birmingham |
Alabama |
|
| City of Hope - Duarte |
Duarte |
California |
|
| University of California Los Angeles |
Los Angeles |
California |
|
| Augusta University Georgia Cancer Center |
Augusta |
Georgia |
|
| Indiana University |
Indianapolis |
Indiana |
|
| Indiana Blood & Marrow Transplantation |
Indianapolis |
Indiana |
|
| University of Kansas Medical Center Research Institute |
Kansas City |
Kansas |
|
| University of Maryland Medical Center |
Baltimore |
Maryland |
|
| Hackensack University Medical Center |
Hackensack |
New Jersey |
|
| Roswell Park Cancer Institute |
Buffalo |
New York |
|
| Monter Cancer Center |
New Hyde Park |
New York |
|
| Stony Brook University Medical Center |
Stony Brook |
New York |
|
| Oregon Health and Science University |
Portland |
Oregon |
|
| The University of Texas MD Anderson Cancer Center |
Houston |
Texas |
|
| Methodist Hospital |
San Antonio |
Texas |
|
| Sanatorio Allende |
Córdoba |
Argentina |
|
| Hospital Privado Centro Medico de Cordoba |
Córdoba |
Argentina |
|
| Royal North Shore Hospital |
Saint Leonards |
New South Wales |
|
| Box Hill Hospital |
Box Hill |
Victoria |
|
| Monash Medical Centre |
Clayton |
Victoria |
|
| Hanusch Krankenhaus Wiener Gebietskrankenkasse |
Vienna |
State of Vienna |
|
| Ordensklinikum Linz Elisabethinen |
Linz |
Upper Austria |
|
| Universitaetsklinik Fuer Innere Medizin I |
Vienna |
Austria |
|
| Hospital Sao Rafael-Monte Tabor |
Salvador |
Estado de Bahia |
|
| Hospital Erasto Gaertner |
Curitiba |
Paraná |
|
| Hospital da Cidade |
Passo Fundo |
Rio Grande do Sul |
|
| Hospital de Clinicas de Porto Alegre |
Porto Alegre |
Rio Grande do Sul |
|
| Hemocentro Campinas Unicamp |
Campinas |
São Paulo |
|
| Fundacao Doutor Amaral Carvalho |
Jaú |
São Paulo |
|
| Hospital das Clinicas da Faculdade de Medicina da Riberao Preto da Universidade de Sao Paulo |
Ribeirão Preto |
São Paulo |
|
| HEMORIO Instituto Estadual de Hematologia Arthur Siqueira de Cavalcanti |
Rio de Janeiro |
Brazil |
|
| Instituto do Cancer do Estado de Sao Paulo |
São Paulo |
Brazil |
|
| Fundacao Antonio Prudente - A.C.Camargo Cancer Center |
São Paulo |
Brazil |
|
| University Multiprofile Hospital for Active Treatment Saint Ivan Rilski |
Sofia |
Sofia |
|
| 855 West 12th Avenue |
Vancouver |
British Columbia |
|
| The Ottawa Hospital |
Ottawa |
Ontario |
|
| Hopital Charles-LeMoyne |
Greenfield Park |
Quebec |
|
| Hopital Maisonneuve-Rosemont |
Montreal |
Quebec |
|
| Henan Cancer Hospital |
Zhengzhou |
Henan |
|
| The First Affiliated Hospital of Soochow University/Suzhou First People's Hospital |
Suzhou |
Jiangsu |
|
+ 52 more sites — see the full list on the official registry below.
More Takeda trials in China