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

A Phase 3, Randomized, Open-label, Multicenter Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)
• Intervention / Treatment: Drug: Ponatinib; Drug: Vincristine; Drug: Dexamethasone; Drug: Cytarabine; Drug: Methotrexate; Drug: Prednisone; Drug: Imatinib

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.

• Study Type: Interventional
• Enrollment (Actual): 245
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Takeda Call center; Phone Number: +1-877-825-3327; Email: medinfoUS@takeda.com

Study Locations

• Argentina
  • Cordoba, Argentina, X5000JHQ
    • Sanatorio Allende
  • Cordoba, Argentina, X5014KEH
    • Hospital Privado Centro Medico de Cordoba
• Australia
  • New South Wales
    • Saint Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
• Austria
  • Vienna, Austria, 1090
    • Universitaetsklinik Fuer Innere Medizin I
  • Upper Austria
    • Linz, Upper Austria, Austria, 4020
      • Ordensklinikum Linz Elisabethinen
  • Vienna
    • Wien, Vienna, Austria, 1140
      • Hanusch Krankenhaus Wiener Gebietskrankenkasse
• Brazil
  • Rio de Janeiro, Brazil, 20211-030
    • HEMORIO Instituto Estadual de Hematologia
  • Sao Paulo, Brazil, 01246-000
    • Instituto do Câncer do Estado de São Paulo
  • Sao Paulo, Brazil, 01509-900
    • Fundacao Antonio Prudente - A.C.Camargo Cancer Center
  • Bahia
    • Salvador, Bahia, Brazil, 41253-190
      • Hospital Sao Rafael-Monte Tabor
  • Parana
    • Curitiba, Parana, Brazil, 81520-060
      • Hospital Erasto Gaertner
  • RIO Grande DO SUL
    • Passo Fundo, RIO Grande DO SUL, Brazil, 99010-260
      • Hospital da Cidade
    • Porto Alegre, RIO Grande DO SUL, Brazil, 90035-003
      • Hospital de Clínicas de Porto Alegre
  • SAO Paulo
    • Campinas, SAO Paulo, Brazil, 130383-878
      • Hemocentro Campinas Unicamp
    • Jau, SAO Paulo, Brazil, 17210-120
      • Fundação Doutor Amaral Carvalho
    • Ribeirao Preto, SAO Paulo, Brazil, 14048-900
      • Hospital das Clinicas da Faculdade de Medicina da Riberao Preto da Universidade de Sao Paulo
• Bulgaria
  • Sofiya
    • Sofia, Sofiya, Bulgaria, 1431
      • University Multiprofile Hospital for Active Treatment Saint Ivan Rilski
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • 855 West 12th Avenue
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hôpital Charles-LeMoyne
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve-Rosemont
• China
  • Tianjin, China, 300041
    • Institute of Hematology & Blood Diseases Hospital of CAMS & PUMC
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University/Suzhou First People's Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University
• Finland
  • Helsinki, Finland, 00029 HUS
    • Helsingin ja Uudenmaan sairaanhoitopiiri
• France
  • Ile-de-france
    • Le Chesnay, Ile-de-france, France, 78157
      • Centre Hospitalier de Versailles Hôpital Andre Mignot
  • Midi-pyrenees
    • Toulouse Cedex 09, Midi-pyrenees, France, 31059
      • Institut Universitaire du Cancer de Toulouse Oncopole
  • PAYS DE LA Loire
    • Angers Cedex 9, PAYS DE LA Loire, France, 49933
      • Center Hospitalier Universitaire d'Angers
  • Rhone-alpes
    • Pierre Benite Cedex, Rhone-alpes, France, 69495
      • Centre Hospitalier Lyon Sud
• Greece
  • Attica
    • Athens, Attica, Greece, 10676
      • Evaggelismos General Hospital
    • Chaidari, Attica, Greece, 12462
      • University General Hospital of Athens Attikon
  • Peloponnese
    • Patra, Peloponnese, Greece, 26504
      • University General Hospital of Patras Panagia I Voithia
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
  • Lecce, Italy, 73100
    • Azienda Ospedaliera Vito Fazzi
  • Milano, Italy, 20132
    • Istituto scientifico universitario San Raffaele
  • Modena, Italy, 41124
    • Azienda Ospedaliero-Universitaria di Modena Policlinico
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
  • Ravenna, Italy, 48121
    • Azienda USL della Romagna
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Roma, Italy, 00161
    • Centro di Ematologia Policlinico Umberto I Universita Sapienza di Roma
  • Forli-cesena
    • Meldola, Forli-cesena, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Azienda Policlinico San Martino
  • Monza E Brianza
    • Monza, Monza E Brianza, Italy, 20090
      • Azienda Ospedaliera San Gerardo di Monza
  • Reggio Nella Emilia
    • Reggio Emilia, Reggio Nella Emilia, Italy, 42123
      • Arcispedale Santa Maria Nuova
  • Venezia
    • Mestre, Venezia, Italy, 30174
      • Ospedale dell'Angelo
• Japan
  • Chiba, Japan, 260-0852
    • Chiba Aoba Municipal Hospital
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 064-0804
      • Aiiku Hospital
  • Kanagawa
    • Isehara City, Kanagawa, Japan, 259-1193
      • Tokai University Hospital
  • Okayama
    • Okayama-shi, Okayama, Japan, 700-8558
      • Okayama University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 48108
    • Inje University Haeundae Paik Hospital
  • Daegu, Korea, Republic of, 42415
    • Yeungnam University Hospital
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, Korea, Republic of, 16247
      • The Catholic University of Korea St. Vincent's Hospital
  • Gyeongsangbuk-do
    • Daegu, Gyeongsangbuk-do, Korea, Republic of, 41944
      • Kyungpook National University Hospital
  • Jeollabuk-do
    • Jeonju, Jeollabuk-do, Korea, Republic of, 54907
      • Chonbuk National University Hospital
• Mexico
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64460
      • Hospital Universitario Dr. Jose Eleuterio Gonzalez
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-367
      • Uniwersytecki Szpital Kliniczny we Wroclawiu
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-501
      • Szpital Uniwersytecki w Krakowie
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-214
      • Uniwersyteckie Centrum Kliniczne
  • Warminsko-mazurskie
    • Olsztyn, Warminsko-mazurskie, Poland, 10-228
      • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurs
• Russian Federation
  • Moscow, Russian Federation, 125167
    • National Research Center for Hematology, Dept. of Hematology/Oncology and BMT
  • Saint Petersburg, Russian Federation, 197341
    • Almazov Federal North-West Medical Research Centre of Department of Health of Russian Federation
  • Moscow CITY
    • Moscow, Moscow CITY, Russian Federation, 127644
      • City Clinical Hospital named after Vikentiy Vikentyevich Veresaev
  • Sverdlovsk
    • Ekaterinburg, Sverdlovsk, Russian Federation, 620102
      • Sverdlovsk Regional Clinical Hospital #1
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Cataluna
    • Badalona, Cataluna, Spain, 08916
      • Institut Català d'Oncologia Badalona - Hospital Germans Trias i Pujol
• Taiwan
  • Hualien
    • Hualien City, Hualien, Taiwan, 970
      • Hualien Tzu Chi Hospital
  • Taichung CITY
    • Taichung, Taichung CITY, Taiwan, 40447
      • China Medical University Hospital
  • Tainan CITY
    • Tainan, Tainan CITY, Taiwan, 70403
      • National Cheng Kung University Hospital
• Turkey
  • Ankara, Turkey, 06590
    • Ankara Universitesi Tp Fakultesi
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • City of Hope - Duarte
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Georgia Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood & Marrow Transplantation
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New Hyde Park, New York, United States, 11042
      • Monter Cancer Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Ponatinib; Ponatinib Tablets.; Other Names: Iclusig; Drug: Vincristine; Vincristine IV injection.; Drug: Dexamethasone; Dexamethasone Tablets.; Drug: Cytarabine; Cytarabine IV infusion.; Drug: Methotrexate; Methotrexate IV infusion.; Drug: Prednisone; Prednisone Tablets.
Active Comparator: 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.	Drug: Vincristine; Vincristine IV injection.; Drug: Dexamethasone; Dexamethasone Tablets.; Drug: Cytarabine; Cytarabine IV infusion.; Drug: Methotrexate; Methotrexate IV infusion.; Drug: Prednisone; Prednisone Tablets.; Drug: Imatinib; Imatinib Tablets.; Other Names: Gleevec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Minimal Residual Disease (MRD)-Negative Complete Remission (CR) at The End of Induction Phase	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).	From Cycle 1 through Cycle 3 (approximately 3 months) (Cycle length = 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of MRD-Negative CR	MRD is defined as the percentage of participants achieving CR who are MRD-negative at multiple intervals after end of induction. MRD negativity: <=0.01% BCR-ABL1/ABL1, or undetectable BCR-ABL1 transcripts in cDNA with >=10,000 ABL1 transcripts. Relapse from CR: Reappearance of blasts in the blood or BM (>=5%) or in any extramedullary site after a CR.	Up to approximately 3 to 6 years
Duration of MRD-Negative CR	Duration of MRD-negative CR is defined as interval between the first assessment at which the criteria for MRD-negative CR are met until the earliest date at which loss of MRD negativity or relapse from CR occurs. MRD negativity (MR4): <=0.01% BCR-ABL1/ABL1, or undetectable BCR-ABL1 transcripts in cDNA with >=10,000 ABL1 transcripts. CR is defined as meeting all the following for at least 4 weeks (that is, no recurrence): 1. No circulating blasts and <5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC >1000/mcL (or >1.0*10^9/L). 5. Platelets >100,000/mcL (or >100*10^9/L). Relapse from CR: Reappearance of blasts in the blood or BM (>=5%) or in any extramedullary site after a CR.	Up to approximately 3 to 6 years
Duration of CR	Duration of CR is defined as interval between the first assessment at which the criteria for CR are met until the earliest date at which relapse from CR occurs. CR is defined as meeting all the following for at least 4 weeks (that is no recurrence): 1. No circulating blasts and <5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC >1000/mcL (or >1.0*10^9/L). 5. Platelets >100,000/mcL (or >100*10^9/L). Relapse from CR: Reappearance of blasts in the blood or BM (>=5%) or in any extramedullary site after a CR.	Up to approximately 3 to 6 years
Time to Treatment Failure	Time to treatment failure is defined as time to end of study randomized treatment (except for hematopoietic stem cell transplantation [HSCT] without loss of MRD-negative CR) due to safety and efficacy reasons. MRD-negative CR is achieved when a participant meets the criteria for both MRD negativity and CR. MRD-negativity: <=0.01% BCR-ABL1/ABL1, or undetectable BCR-ABL1 transcripts in 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 <5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC >1000/mcL (or >1.0*10^9/L). 5. Platelets >100,000/mcL (or >100*10^9/L).	Up to approximately 6 years
Duration of MR4.5	Duration of MR4.5 is defined as interval between the first assessment at which the criteria for MR4.5 are met until the earliest date at which loss of MR4.5 occurs. MR4.5 is molecular response 4.5-log reduction (<=0.0032% BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in cDNA with >=32,000 ABL1 transcripts.	Up to approximately 3 to 6 years
Overall Survival (OS)	OS is defined as interval between the randomization and death due to any cause, censored at the last contact date when the participant was alive.	Up to approximately 3 to 6 years
Event-free Survival (EFS)	EFS is defined as the dates of randomization until death due to any cause or failure to achieve CR by end of induction or relapse from CR. 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) greater than (>) 1000 per micro liter (/mcL) (or >1.0*10^9/L). 5. Platelets >100,000/mcL (or >100*10^9/L).Relapse from CR: reappearance of blasts in the blood or BM (>=5%) or in any extramedullary site after a CR.	Baseline up to approximately 3 to 6 years
Percentage of Participants With CR and Incomplete Complete Remission (CRi)	CR is defined as meeting all the following for at least 4 weeks (that is, no recurrence): 1. No circulating blasts and <5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC >1000/mcL (or >1.0*10^9/L). 5. Platelets >100,000/mcL (or >100*10^9/L). CRi is defined as hematologic complete remission with incomplete hematologic recovery and meeting all criteria for CR except platelet count and/or ANC.	End of Cycle 1 (approximately 1 month), Cycle 2 (approximately 2 months), Cycle 3 (approximately 3 months), and Cycle 9 (approximately 9 months) (Cycle length= 28 days)
Percentage of Participants With Molecular Response	Molecule response is assessed by 3-Log Reduction (MR3), Molecular Response 4-Log Reduction (MR4) and Molecular Response 4.5-Log Reduction (MR4.5). MR3 is defined as molecular response 3-log reduction (<=0.1% BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in cDNA with >=1000 ABL1 transcripts. MR4 is defined as molecular response 4-log reduction (<=0.01% BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in cDNA with >=10,000 ABL1 transcripts. MR4.5 is defined as Molecular response 4.5-log reduction (<=0.0032% BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in cDNA with >=32,000 ABL1 transcripts.	End of Cycle 1 (approximately 1 month), Cycle 2 (approximately 2 months), Cycle 3 (approximately 3 months), and Cycle 9 (approximately 9 months) (Cycle length= 28 days)
Percentage of Participants With Primary Induction Failure (PIF)	PIF is defined as participants who received treatment for ALL but never achieved CR or CRi by the end of induction. PIF is not limited by the number of unsuccessful treatments; this disease status only applies to recipients who have never been in CR or CRi. CR is defined as meeting all the following for at least 4 weeks (that is no recurrence): 1. No circulating blasts and <5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC >1000/mcL (or >1.0*10^9/L). 5. Platelets >100,000/mcL (or >100*10^9/L). CRi is defined as hematologic complete remission with incomplete hematologic recovery and meeting all criteria for CR except platelet count and/or ANC.	Up to 3 months
Percentage of Participants With Overall Response Rate (ORR)	ORR is defined as CR + CRi by end of induction. CR is defined as meeting all the following for at least 4 weeks (that is no recurrence): 1. No circulating blasts and <5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC >1000/mcL (or >1.0*10^9/L). 5. Platelets >100,000/mcL (or >100*10^9/L). CRi is defined as hematologic complete remission with incomplete hematologic recovery and meeting all criteria for CR except platelet count and/or ANC.	Up to 3 months
Percentage of On-Study Participants With Overall Survival (OS)	On-study participants with or without HSCT will be evaluated. OS is defined as interval between randomization and death due to any cause, censored at the last contact date when the participant was alive.	Up to approximately 3 to 6 years
Percentage of On-Study Participants With Relapse From CR	On-study participants with or without HSCT will be evaluated. Relapse from CR is defined as reappearance of blasts in the blood or BM (>=5%) or in any extramedullary site after a CR.	Up to approximately 3 to 6 years

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2018
• Primary Completion (Actual): August 12, 2022
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: July 5, 2018
• First Submitted That Met QC Criteria: July 5, 2018
• First Posted (Actual): July 17, 2018

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Gleevec; Imatinib mesylate; Ponatinib; Bcr-Abl Tyrosine Kinase; Bcr-abl fusion proteins; Iclusig
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Chromosome Aberrations; Translocation, Genetic; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Philadelphia Chromosome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Dermatologic Agents; Protein Kinase Inhibitors; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Dexamethasone; Prednisone; Cytarabine; Methotrexate; Vincristine; Imatinib Mesylate; Ponatinib
• Other Study ID Numbers: Ponatinib-3001; 2018-000397-30 (EudraCT Number); U1111-1206-2370 (Other Identifier: World Health Organization); HC6-24-c220300 (Registry Identifier: Health Canada); jRCT2031210230 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No