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

NCT ID: NCT03589326

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 245 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-04
• Study Completion Date: 2027-07-31

Brief 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.

Detailed 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the primary endpoint, have experienced relapse from CR or have progressive disease, have an unacceptable toxicity, have withdrawn consent, have proceeded to HSCT, or until the sponsor terminates the study, whichever occurs first.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.

Conditions

Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: Ponatinib 30 milligram (mg)

Ponatinib 30 mg, tablets, orally, once daily (QD), with vincristine 1.4 mg/m\^2 (max 2 mg) 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, Days 11 to 14 for up to 3 cycles (each cycle=28 days) in induction phase (reduced dose of ponatinib 15 mg upon achievement of MRD-negative CR at end of induction) followed by ponatinib last induction phase dose with cytarabine, 1000 mg/m\^2 as 2-hour IV infusion (\<60 yrs) and 250 mg/m\^2 (≥60 yrs) every 12 hours, IV on Days 1, 3, 5 of Cycles 2,4,6 and methotrexate, 1000 mg/m\^2 (\<60 yrs) and 250 mg/m\^2 (≥60 yrs), IV infusion, on Day 1 of cycles 1, 3, 5 in consolidation phase followed by ponatinib last consolidation phase dose 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 to 5 for up to 11 cycles in maintenance phase up to data cut-off date: 12 August 2022.

Group Type: EXPERIMENTAL

Ponatinib

Intervention Type: DRUG

Ponatinib Tablets.

Vincristine

Intervention Type: DRUG

Vincristine IV injection.

Dexamethasone

Intervention Type: DRUG

Dexamethasone Tablets.

Cytarabine

Intervention Type: DRUG

Cytarabine IV infusion.

Methotrexate

Intervention Type: DRUG

Methotrexate IV infusion.

Prednisone

Intervention Type: DRUG

Prednisone Tablets.

Cohort B: Imatinib 600 mg

Imatinib 600 mg, tablets, orally, QD, 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 to 4 and Days 11 to 14 in each 28-day cycle for up to 3 cycles in the induction phase followed by imatinib 600 mg, 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 each 28-day even cycles (Cycles 2, 4, and 6), 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 up to data cut-off date: 12 August 2022.

Group Type: ACTIVE_COMPARATOR

Imatinib

Intervention Type: DRUG

Imatinib Tablets.

Vincristine

Intervention Type: DRUG

Vincristine IV injection.

Dexamethasone

Intervention Type: DRUG

Dexamethasone Tablets.

Cytarabine

Intervention Type: DRUG

Cytarabine IV infusion.

Methotrexate

Intervention Type: DRUG

Methotrexate IV infusion.

Prednisone

Intervention Type: DRUG

Prednisone Tablets.

Interventions

Ponatinib

Ponatinib Tablets.

Intervention Type: DRUG

Imatinib

Imatinib Tablets.

Intervention Type: DRUG

Vincristine

Vincristine IV injection.

Intervention Type: DRUG

Dexamethasone

Dexamethasone Tablets.

Intervention Type: DRUG

Cytarabine

Cytarabine IV infusion.

Intervention Type: DRUG

Methotrexate

Methotrexate IV infusion.

Intervention Type: DRUG

Prednisone

Prednisone Tablets.

Intervention Type: DRUG

Other Intervention Names

Iclusig; Gleevec

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

City of Hope - Duarte

Duarte, California, United States

University of California Los Angeles

Los Angeles, California, United States

Augusta University Georgia Cancer Center

Augusta, Georgia, United States

Indiana University

Indianapolis, Indiana, United States

Indiana Blood & Marrow Transplantation

Indianapolis, Indiana, United States

University of Kansas Medical Center Research Institute

Kansas City, Kansas, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Monter Cancer Center

New Hyde Park, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

Oregon Health and Science University

Portland, Oregon, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Methodist Hospital

San Antonio, Texas, United States

Sanatorio Allende

Córdoba, , Argentina

Hospital Privado Centro Medico de Cordoba

Córdoba, , Argentina

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Ordensklinikum Linz Elisabethinen

Linz, Upper Austria, Austria

Hanusch Krankenhaus Wiener Gebietskrankenkasse

Vienna, Vienna, Austria

Universitaetsklinik Fuer Innere Medizin I

Vienna, , Austria

Hospital Sao Rafael-Monte Tabor

Salvador, Estado de Bahia, Brazil

Hospital Erasto Gaertner

Curitiba, Paraná, Brazil

Hospital da Cidade

Passo Fundo, Rio Grande do Sul, Brazil

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hemocentro Campinas Unicamp

Campinas, São Paulo, Brazil

Fundacao Doutor Amaral Carvalho

Jaú, São Paulo, Brazil

Hospital das Clinicas da Faculdade de Medicina da Riberao Preto da Universidade de Sao Paulo

Ribeirão Preto, São Paulo, Brazil

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, Bulgaria

855 West 12th Avenue

Vancouver, British Columbia, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

Hopital Charles-LeMoyne

Greenfield Park, Quebec, Canada

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Henan Cancer Hospital

Zhengzhou, Henan, China

The First Affiliated Hospital of Soochow University/Suzhou First People's Hospital

Suzhou, Jiangsu, China

The First Hospital of Jilin University

Changchun, Jilin, China

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, China

Institute of Hematology & Blood Diseases Hospital of CAMS & PUMC

Tianjin, , China

Helsingin ja Uudenmaan sairaanhoitopiiri

Helsinki, , Finland

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, Midi-pyrenees, France

Center Hospitalier Universitaire d'Angers

Angers, Pays de la Loire Region, France

Centre Hospitalier de Versailles Hopital Andre Mignot

Le Chesnay, Île-de-France Region, France

University General Hospital of Athens Attikon

Chaïdári, Attica, Greece

Evaggelismos General Hospital

Athens, Ipsiladou 45-47, Greece

General University Hospital of Patras Panagia I Voithia

Pátrai, Rio, Greece

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli-cesena, Italy

Azienda Policlinico San Martino

Genoa, Liguria, Italy

Azienda Ospedaliera San Gerardo di Monza

Monza, Monza E Brianza, Italy

Arcispedale Santa Maria Nuova

Reggio Emilia, Reggio Nella Emilia, Italy

Ospedale dell'Angelo

Mestre, Venezia, Italy

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, , Italy

Azienda Ospedaliera Vito Fazzi

Lecce, , Italy

Istituto Scientifico Universitario San Raffaele

Milan, , Italy

Azienda Ospedaliero-Universitaria di Modena Policlinico

Modena, , Italy

Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello

Palermo, , Italy

Azienda USL della Romagna

Ravenna, , Italy

Centro di Ematologia Policlinico Umberto I Universita Sapienza di Roma

Roma, , Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, , Italy

Chiba Aoba Municipal Hospital

Chiba, Chiba, Japan

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Fukushima Medical University Hospital

Fukushima, Fukushima, Japan

Aiiku Hospital

Sapporo, Hokkaido, Japan

Tokai University Hospital

Isehara, Kanagawa, Japan

Okayama University Hospital

Okayama, Okayama-ken, Japan

Hospital Universitario Dr. Jose Eleuterio Gonzalez

Monterrey, Nuevo León, Mexico

Szpital Uniwersytecki w Krakowie

Krakow, Lesser Poland Voivodeship, Poland

Uniwersytecki Szpital Kliniczny we Wroclawiu

Wroclaw, Lower Silesian Voivodeship, Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurs

Olsztyn, Warmian-Masurian Voivodeship, Poland

City Clinical Hospital named after Vikentiy Vikentyevich Veresaev

Moscow, Moscow CITY, Russia

Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, Sverdlovsk Oblast, Russia

National Research Center for Hematology, Dept. of Hematology/Oncology and BMT

Moscow, , Russia

Almazov Federal North-West Medical Research Centre of Department of Health of Russian Federation

Saint Petersburg, , Russia

The Catholic University of Korea St. Vincent's Hospital

Suwon, Gyeonggi-do, South Korea

Kyungpook National University Hospital

Daegu, Gyeongsangbuk-do, South Korea

Chonbuk National University Hospital

Jeonju, Jeollabuk-do, South Korea

Inje University Haeundae Paik Hospital

Busan, , South Korea

Yeungnam University Hospital

Daegu, , South Korea

Institut Catala d'Oncologia Badalona - Hospital Germans Trias i Pujol

Badalona, Catalonia, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Hualien Tzu Chi Hospital

Hualien City, Hualien, Taiwan

China Medical University Hospital

Taichung, Taichung CITY, Taiwan

National Cheng Kung University Hospital

Tainan, Tainan CITY, Taiwan

Ankara Universitesi Tp Fakultesi

Ankara, , Turkey (Türkiye)

Countries

United States; Argentina; Australia; Austria; Brazil; Bulgaria; Canada; China; Finland; France; Greece; Italy; Japan; Mexico; Poland; Russia; South Korea; Spain; Taiwan; Turkey (Türkiye)

References

Ashaye A, Shi L, Aldoss I, Montesinos P, Vachhani P, Rocha V, Papayannidis C, Leonard JT, Baer MR, Ribera JM, McCloskey J, Wang J, Rane D, Guo S. Quality-Adjusted Time Without Symptoms of Disease or Toxicity (Q-TWiST) in Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Comparison of Ponatinib Versus Imatinib. Cancer Med. 2025 Apr;14(7):e70780. doi: 10.1002/cam4.70780.

Reference Type: DERIVED

PMID: 40165400 (View on PubMed)

Jabbour E, Kantarjian HM, Aldoss I, Montesinos P, Leonard JT, Gomez-Almaguer D, Baer MR, Gambacorti-Passerini C, McCloskey J, Minami Y, Papayannidis C, Rocha V, Rousselot P, Vachhani P, Wang ES, Wang B, Hennessy M, Vorog A, Patel N, Yeh T, Ribera JM. Ponatinib vs Imatinib in Frontline Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2024 Jun 4;331(21):1814-1823. doi: 10.1001/jama.2024.4783.

Reference Type: DERIVED

PMID: 38722621 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1206-2370

Identifier Type: OTHER

Identifier Source: secondary_id

HC6-24-c220300

Identifier Type: REGISTRY

Identifier Source: secondary_id

jRCT2031210230

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-508463-71-00

Identifier Type: CTIS

Identifier Source: secondary_id

Ponatinib-3001

Identifier Type: -

Identifier Source: org_study_id