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

• ClinicalTrials.gov Identifier: NCT03589326
• Recruitment Status: Active, not recruiting
• First Posted: July 17, 2018
• Results First Posted: October 27, 2023
• Last Update Posted: October 27, 2023
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)	Drug: Ponatinib; Drug: Imatinib; Drug: Vincristine; Drug: Dexamethasone; Drug: Cytarabine; Drug: Methotrexate; Drug: Prednisone	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 245 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: It is an open-label trial, therefore investigators and participants are unblinded.
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: October 4, 2018
• Actual Primary Completion Date: August 12, 2022
• Estimated Study Completion Date: July 31, 2027

Arms and Interventions

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 Name: 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: Imatinib; Imatinib Tablets.; Other Name: Gleevec; Drug: Vincristine; Vincristine IV injection.; Drug: Dexamethasone; Dexamethasone Tablets.; Drug: Cytarabine; Cytarabine IV infusion.; Drug: Methotrexate; Methotrexate IV infusion.; Drug: Prednisone; Prednisone Tablets.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Minimal Residual Disease (MRD)-Negative Complete Remission (CR) at The End of Induction Phase [ Time Frame: 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).

Secondary Outcome Measures :

1. Event-free Survival (EFS) [ Time Frame: Baseline up to approximately 3 to 6 years ]
   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.
2. Percentage of Participants With CR and Incomplete Complete Remission (CRi) [ Time Frame: 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) ]
   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.
3. Percentage of Participants With Molecular Response [ Time Frame: 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) ]
   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.
4. Percentage of Participants With Primary Induction Failure (PIF) [ Time Frame: Up to 3 months ]
   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.
5. Percentage of Participants With Overall Response Rate (ORR) [ Time Frame: Up to 3 months ]
   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.
6. Percentage of MRD-Negative CR [ Time Frame: Up to approximately 3 to 6 years ]
   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.
7. Duration of MRD-Negative CR [ Time Frame: Up to approximately 3 to 6 years ]
   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.
8. Duration of CR [ Time Frame: Up to approximately 3 to 6 years ]
   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.
9. Time to Treatment Failure [ Time Frame: Up to approximately 6 years ]
   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).
10. Duration of MR4.5 [ Time Frame: Up to approximately 3 to 6 years ]
    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.
11. Percentage of On-Study Participants With Overall Survival (OS) [ Time Frame: Up to approximately 3 to 6 years ]
    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.
12. Percentage of On-Study Participants With Relapse From CR [ Time Frame: Up to approximately 3 to 6 years ]
    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.
13. Overall Survival (OS) [ Time Frame: Up to approximately 3 to 6 years ]
    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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, California

City of Hope - Duarte

Duarte, California, United States, 91010

University of California Los Angeles

Los Angeles, California, United States, 90095

United States, Georgia

Augusta University Georgia Cancer Center

Augusta, Georgia, United States, 30912

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

Indiana Blood & Marrow Transplantation

Indianapolis, Indiana, United States, 46237

United States, Kansas

University of Kansas Medical Center Research Institute

Kansas City, Kansas, United States, 66160

United States, Maryland

University of Maryland Medical Center

Baltimore, Maryland, United States, 21201

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

Monter Cancer Center

New Hyde Park, New York, United States, 11042

Stony Brook University Medical Center

Stony Brook, New York, United States, 11794

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Texas

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Methodist Hospital

San Antonio, Texas, United States, 78229

Argentina

Sanatorio Allende

Cordoba, Argentina, X5000JHQ

Hospital Privado Centro Medico de Cordoba

Cordoba, Argentina, X5014KEH

Australia, New South Wales

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia, 2065

Australia, Victoria

Box Hill Hospital

Box Hill, Victoria, Australia, 3128

Monash Medical Centre

Clayton, Victoria, Australia, 3168

Austria

Ordensklinikum Linz Elisabethinen

Linz, Upper Austria, Austria, 4020

Hanusch Krankenhaus Wiener Gebietskrankenkasse

Wien, Vienna, Austria, 1140

Universitaetsklinik Fuer Innere Medizin I

Vienna, Austria, 1090

Brazil

Hospital Sao Rafael-Monte Tabor

Salvador, Bahia, Brazil, 41253-190

Hospital Erasto Gaertner

Curitiba, Parana, Brazil, 81520-060

Hospital da Cidade

Passo Fundo, RIO Grande DO SUL, Brazil, 99010-260

Hospital de Clinicas de Porto Alegre

Porto Alegre, RIO Grande DO SUL, Brazil, 90035-003

Hemocentro Campinas Unicamp

Campinas, SAO Paulo, Brazil, 130383-878

Fundacao Doutor Amaral Carvalho

Jau, SAO Paulo, Brazil, 17210-120

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

Ribeirao Preto, SAO Paulo, Brazil, 14048-900

HEMORIO Instituto Estadual de Hematologia

Rio de Janeiro, Brazil, 20211-030

Instituto do Cancer do Estado de Sao Paulo

Sao Paulo, Brazil, 01246-000

Fundacao Antonio Prudente - A.C.Camargo Cancer Center

Sao Paulo, Brazil, 01509-900

Bulgaria

University Multiprofile Hospital for Active Treatment Saint Ivan Rilski

Sofia, Sofiya, Bulgaria, 1431

Canada, British Columbia

855 West 12th Avenue

Vancouver, British Columbia, Canada, V5Z 1M9

Canada, Ontario

The Ottawa Hospital

Ottawa, Ontario, Canada, K1H 8L6

Canada, Quebec

Hopital Charles-LeMoyne

Greenfield Park, Quebec, Canada, J4V 2H1

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada, H1T 2M4

China, Henan

Henan Cancer Hospital

Zhengzhou, Henan, China, 450008

China, Jiangsu

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

Suzhou, Jiangsu, China, 215006

China, Jilin

The First Hospital of Jilin University

Changchun, Jilin, China, 130021

China, Zhejiang

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, China, 310003

China

Institute of Hematology & Blood Diseases Hospital of CAMS & PUMC

Tianjin, China, 300041

Finland

Helsingin ja Uudenmaan sairaanhoitopiiri

Helsinki, Finland, 00029 HUS

France

Centre Hospitalier de Versailles Hopital Andre Mignot

Le Chesnay, Ile-de-france, France, 78157

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse Cedex 09, Midi-pyrenees, France, 31059

Center Hospitalier Universitaire d'Angers

Angers Cedex 9, PAYS DE LA Loire, France, 49933

Centre Hospitalier Lyon Sud

Pierre Benite Cedex, Rhone-alpes, France, 69495

Greece

Evaggelismos General Hospital

Athens, Attica, Greece, 10676

University General Hospital of Athens Attikon

Chaidari, Attica, Greece, 12462

University General Hospital of Patras Panagia I Voithia

Patra, Peloponnese, Greece, 26504

Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli-cesena, Italy, 47014

Azienda Policlinico San Martino

Genova, Liguria, Italy, 16132

Azienda Ospedaliera San Gerardo di Monza

Monza, Monza E Brianza, Italy, 20090

Arcispedale Santa Maria Nuova

Reggio Emilia, Reggio Nella Emilia, Italy, 42123

Ospedale dell'Angelo

Mestre, Venezia, Italy, 30174

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, Italy, 40138

Azienda Ospedaliera Vito Fazzi

Lecce, Italy, 73100

Istituto Scientifico Universitario San Raffaele

Milano, Italy, 20132

Azienda Ospedaliero-Universitaria di Modena Policlinico

Modena, Italy, 41124

Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello

Palermo, Italy, 90146

Azienda USL della Romagna

Ravenna, Italy, 48121

Centro di Ematologia Policlinico Umberto I Universita Sapienza di Roma

Roma, Italy, 00161

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy, 00168

Japan

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan, 277-8577

Aiiku Hospital

Sapporo, Hokkaido, Japan, 064-0804

Tokai University Hospital

Isehara City, Kanagawa, Japan, 259-1193

Okayama University Hospital

Okayama-shi, Okayama, Japan, 700-8558

Chiba Aoba Municipal Hospital

Chiba, Japan, 260-0852

Fukushima Medical University Hospital

Fukushima, Japan, 960-1295

Korea, Republic of

The Catholic University of Korea St. Vincent's Hospital

Suwon, Gyeonggi-do, Korea, Republic of, 16247

Kyungpook National University Hospital

Daegu, Gyeongsangbuk-do, Korea, Republic of, 41944

Chonbuk National University Hospital

Jeonju, Jeollabuk-do, Korea, Republic of, 54907

Inje University Haeundae Paik Hospital

Busan, Korea, Republic of, 48108

Yeungnam University Hospital

Daegu, Korea, Republic of, 42415

Mexico

Hospital Universitario Dr. Jose Eleuterio Gonzalez

Monterrey, Nuevo LEON, Mexico, 64460

Poland

Uniwersytecki Szpital Kliniczny we Wroclawiu

Wroclaw, Dolnoslaskie, Poland, 50-367

Szpital Uniwersytecki w Krakowie

Krakow, Malopolskie, Poland, 31-501

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomorskie, Poland, 80-214

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

Olsztyn, Warminsko-mazurskie, Poland, 10-228

Russian Federation

City Clinical Hospital named after Vikentiy Vikentyevich Veresaev

Moscow, Moscow CITY, Russian Federation, 127644

Sverdlovsk Regional Clinical Hospital #1

Ekaterinburg, Sverdlovsk, Russian Federation, 620102

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

Moscow, Russian Federation, 125167

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

Saint Petersburg, Russian Federation, 197341

Spain

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

Badalona, Cataluna, Spain, 08916

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Hospital Universitario de Salamanca

Salamanca, Spain, 37007

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Spain, 46026

Taiwan

Hualien Tzu Chi Hospital

Hualien City, Hualien, Taiwan, 970

China Medical University Hospital

Taichung, Taichung CITY, Taiwan, 40447

National Cheng Kung University Hospital

Tainan, Tainan CITY, Taiwan, 70403

Turkey

Ankara Universitesi Tp Fakultesi

Ankara, Turkey, 06590

Sponsors and Collaborators

Takeda

Investigators

• Study Director: Study Director; Takeda

  Study Documents (Full-Text)

Documents provided by Takeda:

Study Protocol  [PDF] October 29, 2021

Statistical Analysis Plan  [PDF] September 20, 2022

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03589326
• 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 )
• First Posted: July 17, 2018
• Results First Posted: October 27, 2023
• Last Update Posted: October 27, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• 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.
• URL: https://vivli.org/ourmember/takeda/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda:

Ponatinib; Imatinib mesylate; Bcr-Abl Tyrosine Kinase; Bcr-abl fusion proteins; Iclusig; Gleevec

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Philadelphia Chromosome; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Translocation, Genetic; Chromosome Aberrations; Pathologic Processes; Cytarabine; Dexamethasone; Prednisone; Methotrexate; Vincristine; Imatinib Mesylate; Ponatinib; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists