Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)Phase 3NCT03589326
A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia
A Phase 3 study testing Ponatinib, Imatinib and Vincristine in people with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL), run by Takeda at 92 sites in 20 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)
- What is being tested?
- Ponatinib, Imatinib and Vincristine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 245 participants
- Where
- 92 sitesin 20 countries
- Study dates
- 4 Oct 2018to 31 Jul 2027
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL, as defined by the 2017 national comprehensive cancer network (NCCN) guidelines.
- Eastern Cooperative Oncology Group (ECOG) performance status of <=2.
Who cannot join
- With a history or current diagnosis of chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML).
- 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.
- 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).
- 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.
- Uncontrolled active serious infection that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Major surgery within 28 days before randomization (minor surgical procedures such as catheter placement or BM biopsy are not exclusionary criteria).
Show all 16Show fewer
- Known human immunodeficiency virus (HIV) seropositivity, known active hepatitis B or C infection.
- History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis.
- Uncontrolled hypertriglyceridemia (triglycerides >450 milligram per deciliter [mg/dL]).
- 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.
- 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.
- Clinical manifestations of CNS or extramedullary involvement with ALL other than lymphadenopathy or hepatosplenomegaly.
- Autoimmune disease with potential CNS involvement.
- Known significant neuropathy of Grade >=2 severity.
- Clinically significant, uncontrolled, or active cardiovascular, cerebrovascular, or peripheral vascular disease, or history of or active venous thrombotic/embolic event (VTE) disease.
- Have a significant bleeding disorder unrelated to ALL.
Trial locations and contacts
92 sites in 20 countries.
92 sites in 20 countries
United States15 sites
Augusta University Georgia Cancer Center
Augusta, Georgia, 30912
University of Maryland Medical Center
Baltimore, Maryland, 21201
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Roswell Park Cancer Institute
Buffalo, New York, 14263
City of Hope - Duarte
Duarte, California, 91010
Hackensack University Medical Center
Hackensack, New Jersey, 07601
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
Indiana Blood & Marrow Transplantation
Indianapolis, Indiana, 46237
University of Kansas Medical Center Research Institute
Kansas City, Kansas, 66160
University of California Los Angeles
Los Angeles, California, 90095
Monter Cancer Center
New Hyde Park, New York, 11042
Oregon Health and Science University
Portland, Oregon, 97239
Methodist Hospital
San Antonio, Texas, 78229
Stony Brook University Medical Center
Stony Brook, New York, 11794
Italy13 sites
Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
Bologna, 40138
Azienda Policlinico San Martino
Genoa, Liguria, 16132
Azienda Ospedaliera Vito Fazzi
Lecce, 73100
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, Forli-cesena, 47014
Ospedale dell'Angelo
Mestre, Venezia, 30174
Istituto Scientifico Universitario San Raffaele
Milan, 20132
Azienda Ospedaliero-Universitaria di Modena Policlinico
Modena, 41124
Azienda Ospedaliera San Gerardo di Monza
Monza, Monza E Brianza, 20090
Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
Palermo, 90146
Azienda USL della Romagna
Ravenna, 48121
Arcispedale Santa Maria Nuova
Reggio Emilia, Reggio Nella Emilia, 42123
Centro di Ematologia Policlinico Umberto I Universita Sapienza di Roma
Roma, 00161
Fondazione Policlinico Universitario Agostino Gemelli
Roma, 00168
Brazil10 sites
Hemocentro Campinas Unicamp
Campinas, São Paulo, 130383-878
Hospital Erasto Gaertner
Curitiba, Paraná, 81520-060
Fundacao Doutor Amaral Carvalho
Jaú, São Paulo, 17210-120
Hospital da Cidade
Passo Fundo, Rio Grande do Sul, 99010-260
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-003
Hospital das Clinicas da Faculdade de Medicina da Riberao Preto da Universidade de Sao Paulo
Ribeirão Preto, São Paulo, 14048-900
HEMORIO Instituto Estadual de Hematologia Arthur Siqueira de Cavalcanti
Rio de Janeiro, 20211-030
Hospital Sao Rafael-Monte Tabor
Salvador, Estado de Bahia, 41253-190
Instituto do Cancer do Estado de Sao Paulo
São Paulo, 01246-000
Fundacao Antonio Prudente - A.C.Camargo Cancer Center
São Paulo, 01509-900
Japan6 sites
Chiba Aoba Municipal Hospital
Chiba, Chiba, 260-0852
Fukushima Medical University Hospital
Fukushima, Fukushima, 960-1295
Tokai University Hospital
Isehara, Kanagawa, 259-1193
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Okayama University Hospital
Okayama, Okayama-ken, 700-8558
Aiiku Hospital
Sapporo, Hokkaido, 064-0804
China5 sites
The First Hospital of Jilin University
Changchun, Jilin, 130021
The First Affiliated Hospital, Zhejiang University
Hangzhou, Zhejiang, 310003
The First Affiliated Hospital of Soochow University/Suzhou First People's Hospital
Suzhou, Jiangsu, 215006
Institute of Hematology & Blood Diseases Hospital of CAMS & PUMC
Tianjin, 300041
Henan Cancer Hospital
Zhengzhou, Henan, 450008
South Korea5 sites
Inje University Haeundae Paik Hospital
Busan, 48108
Kyungpook National University Hospital
Daegu, Gyeongsangbuk-do, 41944
Yeungnam University Hospital
Daegu, 42415
Chonbuk National University Hospital
Jeonju, Jeollabuk-do, 54907
The Catholic University of Korea St. Vincent's Hospital
Suwon, Gyeonggi-do, 16247
Canada4 sites
Hopital Charles-LeMoyne
Greenfield Park, Quebec, J4V 2H1
Hopital Maisonneuve-Rosemont
Montreal, Quebec, H1T 2M4
The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
855 West 12th Avenue
Vancouver, British Columbia, V5Z 1M9
France4 sites
Center Hospitalier Universitaire d'Angers
Angers, Pays de la Loire Region, 49933
Centre Hospitalier de Versailles Hopital Andre Mignot
Le Chesnay, Île-de-France Region, 78157
Centre Hospitalier Lyon Sud
Pierre-Bénite, Auvergne-Rhône-Alpes, 69495
Institut Universitaire du Cancer de Toulouse Oncopole
Toulouse, Midi-pyrenees, 31059
Poland4 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomeranian Voivodeship, 80-214
Szpital Uniwersytecki w Krakowie
Krakow, Lesser Poland Voivodeship, 31-501
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurs
Olsztyn, Warmian-Masurian Voivodeship, 10-228
Uniwersytecki Szpital Kliniczny we Wroclawiu
Wroclaw, Lower Silesian Voivodeship, 50-367
Russia4 sites
City Clinical Hospital named after Vikentiy Vikentyevich Veresaev
Moscow, Moscow CITY, 127644
National Research Center for Hematology, Dept. of Hematology/Oncology and BMT
Moscow, 125167
Almazov Federal North-West Medical Research Centre of Department of Health of Russian Federation
Saint Petersburg, 197341
Sverdlovsk Regional Clinical Hospital #1
Yekaterinburg, Sverdlovsk Oblast, 620102
Spain4 sites
Institut Catala d'Oncologia Badalona - Hospital Germans Trias i Pujol
Badalona, Catalonia, 08916
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Universitario de Salamanca
Salamanca, 37007
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Australia3 sites
Box Hill Hospital
Box Hill, Victoria, 3128
Monash Medical Centre
Clayton, Victoria, 3168
Royal North Shore Hospital
Saint Leonards, New South Wales, 2065
Austria3 sites
Ordensklinikum Linz Elisabethinen
Linz, Upper Austria, 4020
Hanusch Krankenhaus Wiener Gebietskrankenkasse
Vienna, State of Vienna, 1140
Universitaetsklinik Fuer Innere Medizin I
Vienna, 1090
Greece3 sites
Evaggelismos General Hospital
Athens, Ipsiladou 45-47, 10676
University General Hospital of Athens Attikon
Chaïdári, Attica, 12462
General University Hospital of Patras Panagia I Voithia
Pátrai, Rio, 26504
Taiwan3 sites
Hualien Tzu Chi Hospital
Hualien City, Hualien, 970
China Medical University Hospital
Taichung, Taichung CITY, 40447
National Cheng Kung University Hospital
Tainan, Tainan CITY, 70403
Argentina2 sites
Sanatorio Allende
Córdoba, X5000JHQ
Hospital Privado Centro Medico de Cordoba
Córdoba, X5014KEH
Bulgaria1 site
University Multiprofile Hospital for Active Treatment Saint Ivan Rilski
Sofia, Sofia, 1431
Mexico1 site
Hospital Universitario Dr. Jose Eleuterio Gonzalez
Monterrey, Nuevo León, 64460
Turkey (Türkiye)1 site
Ankara Universitesi Tp Fakultesi
Ankara, 06590
About this study
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)
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.
Read the 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.
- Being tested
- Ponatinib, Imatinib, Vincristine, Dexamethasone, Cytarabine
- Keywords
- Ponatinib, Imatinib mesylate, Bcr-Abl Tyrosine Kinase, Bcr-abl fusion proteins, Iclusig, Gleevec
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PonatinibDrug
Also called Iclusig
Ponatinib Tablets.
ImatinibDrug
Also called Gleevec
Imatinib Tablets.
VincristineDrug
Vincristine IV injection.
DexamethasoneDrug
Dexamethasone Tablets.
CytarabineDrug
Cytarabine IV infusion.
MethotrexateDrug
Methotrexate IV infusion.
PrednisoneDrug
Prednisone Tablets.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Ponatinib 30 milligram (mg) | Experimental | 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. Receives: Drug: Ponatinib; Drug: Vincristine; Drug: Dexamethasone; Drug: Cytarabine; Drug: Methotrexate; Drug: Prednisone |
| Cohort B: Imatinib 600 mg | Active comparator | 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. Receives: Drug: Imatinib; Drug: Vincristine; Drug: Dexamethasone; Drug: Cytarabine; Drug: Methotrexate; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From Cycle 1 through Cycle 3 (approximately 3 months) (Cycle length = 28 days)
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 3 months
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Up to approximately 3 to 6 years
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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 3 to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2018
- Study start4 Oct 2018
- Primary completion12 Aug 2022
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)Studies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 245 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03589326
- Sponsor's protocol ID
- Ponatinib-3001
- Other IDs
- U1111-1206-2370, HC6-24-c220300, jRCT2031210230, 2023-508463-71-00, 2023
- Status last verified
- Nov 2025
- First submitted
- 5 Jul 2018
- Last updated
- 26 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 40165400Hanley MJ, Larson TR, Diderichsen PM, Largajolli A, Hui K, Srimani J, Wang B, Vorog A, Gupta N. Population Pharmacokinetic and Exposure-Response Analyses for Ponatinib in the Phase 3 PhALLCON Study. Clin Transl Sci. 2025 Mar;18(3):e70175. doi: 10.1111/cts.70175.
PubMed 40025846Jabbour 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.
PubMed 38722621
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03589326
- Acronym / sponsor ID
- Ponatinib-3001
- Keywords
- Ponatinib, Imatinib mesylate, Bcr-Abl Tyrosine Kinase, Bcr-abl fusion proteins, Iclusig, Gleevec
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 245 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 4 Oct 2018 (actual)
- Primary completion
- 12 Aug 2022 (actual)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 17 Jul 2018 (actual)
- Results
- Posted 27 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Ponatinib 30 milligram (mg) | Experimental | Drug: Ponatinib, Drug: Vincristine, Drug: Dexamethasone, Drug: Cytarabine, Drug: Methotrexate, Drug: PrednisonePonatinib 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. |
| Cohort B: Imatinib 600 mg | Active comparator | Drug: Imatinib, Drug: Vincristine, Drug: Dexamethasone, Drug: Cytarabine, Drug: Methotrexate, Drug: PrednisoneImatinib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Newly diagnosed Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL, as defined by the 2017 national comprehensive cancer network (NCCN) guidelines.
- Eastern Cooperative Oncology Group (ECOG) performance status of <=2.
Key exclusion criteria (16 listed)
- With a history or current diagnosis of chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML).
- 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.
- 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).
- 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.
- Uncontrolled active serious infection that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PonatinibAlso: IclusigPonatinib Tablets. | Drug | Cohort A: Ponatinib 30 milligram (mg) |
| ImatinibAlso: GleevecImatinib Tablets. | Drug | Cohort B: Imatinib 600 mg |
| VincristineVincristine IV injection. | Drug | Cohort A: Ponatinib 30 milligram (mg), Cohort B: Imatinib 600 mg |
| DexamethasoneDexamethasone Tablets. | Drug | Cohort A: Ponatinib 30 milligram (mg), Cohort B: Imatinib 600 mg |
| CytarabineCytarabine IV infusion. | Drug | Cohort A: Ponatinib 30 milligram (mg), Cohort B: Imatinib 600 mg |
| MethotrexateMethotrexate IV infusion. | Drug | Cohort A: Ponatinib 30 milligram (mg), Cohort B: Imatinib 600 mg |
| PrednisonePrednisone Tablets. | Drug | Cohort A: Ponatinib 30 milligram (mg), Cohort B: Imatinib 600 mg |
Primary outcome
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).
13 secondary outcomes
Event-free Survival (EFS)
Time frame: Baseline up to approximately 3 to 6 years
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)
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)
Percentage of Participants With Primary Induction Failure (PIF)
Time frame: Up to 3 months
Percentage of Participants With Overall Response Rate (ORR)
Time frame: Up to 3 months
Percentage of MRD-Negative CR
Time frame: Up to approximately 3 to 6 years
Duration of MRD-Negative CR
Time frame: Up to approximately 3 to 6 years
Duration of CR
Time frame: Up to approximately 3 to 6 years
Time to Treatment Failure
Time frame: Up to approximately 6 years
Duration of MR4.5
Time frame: Up to approximately 3 to 6 years
Percentage of On-Study Participants With Overall Survival (OS)
Time frame: Up to approximately 3 to 6 years
Percentage of On-Study Participants With Relapse From CR
Time frame: Up to approximately 3 to 6 years
Overall Survival (OS)
Time frame: Up to approximately 3 to 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40165400Ashaye 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.
- Derived from this study: PubMed 40025846Hanley MJ, Larson TR, Diderichsen PM, Largajolli A, Hui K, Srimani J, Wang B, Vorog A, Gupta N. Population Pharmacokinetic and Exposure-Response Analyses for Ponatinib in the Phase 3 PhALLCON Study. Clin Transl Sci. 2025 Mar;18(3):e70175. doi: 10.1111/cts.70175.
- Derived from this study: PubMed 38722621Jabbour 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
92 sites in 20 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ponatinib, Imatinib and Vincristine in people with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL), run by Takeda at 92 sites in 20 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 92 sites in United States, Italy, Brazil, Japan, China and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03589326, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2025.