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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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