AzTrials
AzTrials

Pediatric Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ALL)Phase 1/2NCT04501614

A Study of Ponatinib With Chemotherapy in Children, Teenagers, and Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

A Phase 1/2 study testing Ponatinib and Chemotherapy Agents in people with Pediatric Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ALL) and Ph+ Mixed Phenotype Acute Leukemia (MPAL), run by Takeda at 64 sites in 15 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This study is about an anticancer drug called ponatinib which is a tyrosine kinase inhibitor given with chemotherapy to children, teenagers, and young adults up to 21 years of age with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia who have relapsed or are resistant to other treatment. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
Ponatinib and Chemotherapy Agents
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
64 sitesin 15 countries
Study dates
24 Feb 2021to 19 Jul 2024
Phase
Phase 1/2
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 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Participants must have a diagnosis of Ph+ ALL, Philadelphia chromosome-positive plus mixed phenotype acute leukemia (Ph+ MPAL), or Ph-like ALL with:
  • Involvement of BM with ALL, including one of the following: i. M2 BM (5%-24% lymphoblasts): by morphology with confirmatory testing consisting of at least one of the following: flow cytometry lymphoblasts ≥5%, or BCR-ABL1 fluorescence in situ hybridization, or ≥10-2 leukemic clone identified by immunoglobulin heavy chain-T-cell receptor polymerase chain reaction, OR ii. M3 BM (≥25% lymphoblasts): by morphology, OR iii. Participants with combined BM (as defined above) and extramedullary disease.
  • Evidence of Ph+ ALL, MPAL, or Ph-like ALL: i. Definite evidence of BCR-ABL1 fusion (Ph) for Ph+ ALL and MPAL, OR ii. Definite evidence of Ph-like ALL with targetable kinase-activating lesions involving any of the following kinase genes: ABL1, ABL2, CSF1R, and PDGFRB.
  • Ph-like ALL diagnosis requires the identification of specified targetable kinase-activating lesions preferably by ribonucleic acid (RNA) sequencing or by alternative accredited method used by the site.
  • Disease status: (i) For non-US sites: participants who have relapsed (post 0 or 1 HSCT) or are resistant or intolerant to at least one prior therapy that contained a BCR-ABL-targeted tyrosine kinase inhibitor (TKI), or for US sites: participants who have relapsed (post 0 or 1 HSCT) or are resistant or intolerant to at least one prior therapy that contained a second-generation BCR-ABL1-targeted TKI (i.e, dasatinib, nilotinib, and bosutinib); OR (ii) Have a BCR-ABL1 T315I mutation irrespective of relapse, resistance/intolerance, or transplant status and irrespective of any prior TKI use.
  • Notes:
Show all 28Show fewer
  • A participant will be defined as intolerant if they had a Grade ≥3 nonhematologic toxicity or a Grade 4 hematologic toxicity considered related to the last TKI and lasting for >2 weeks, and led to discontinuation of therapy.
  • Weight: Participants must be weighing at least 5 kg at the time of enrollment.
  • Performance Status: Karnofsky performance status ≥50% for participants ≥16 years of age or Lansky Play Scale ≥50% for participants <16 years of age.
  • Have recovered to less than Grade 2 National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) Version 5.0, or to baseline, from any nonhematologic toxicities (except alopecia) due to previous therapy.
  • Participants must meet the following criteria related to prior therapies:
  • Cytoreduction with hydroxyurea: Hydroxyurea can be initiated and continued for up to 24 hours before the start of protocol therapy.
  • Participants who relapsed while receiving cytotoxic therapy: At least 14 days must have passed since the completion of the last dose of chemotherapy before the first dose of ponatinib can be given except for the following: intrathecal (IT) chemotherapy and/or maintenance therapy such as vincristine, mercaptopurine, methotrexate, or glucocorticoids. There is no waiting period for those relapsing on maintenance-like therapy.
  • HSCT: Participants who have experienced relapse after a HSCT are eligible, provided they have no evidence of acute or chronic graft-versus-host disease (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 90 days posttransplant at the time of enrollment.
  • Hematopoietic growth factors: Before the first dose of ponatinib, at least 7 days must have passed since completion of therapy with granulocyte colony-stimulating factor or other growth factors, and at least 14 days must have passed since completion of therapy with pegfilgrastim.
  • Biologics and targeted therapies: Before the first dose of ponatinib, at least 7 days must have passed since the last dose of a biologic agent. For agents that have known AEs occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur. The duration of this interval must be discussed with the sponsor's medical monitor/designee.
  • Monoclonal antibodies: After the last dose of monoclonal antibody, at least 3 half-lives of the administered antibody must have passed before the first dose of ponatinib.
  • Immunotherapy: Before the first dose of ponatinib, at least 30 days must have passed after the completion of any type of immunotherapy (eg, tumor vaccines, chimeric antigen receptor T-cell [CAR-T-cell]).
  • Immunosuppressive therapy: Before the first dose of ponatinib, at least 14 days must have passed after the completion of immunosuppressive therapy (including regimens following stem cell transplant).
  • Radiotherapy: No washout period is necessary for radiation given to any extramedullary site other than central nervous system (CNS); ≥90 days must have passed if participant received prior total body irradiation or craniospinal or cranial radiotherapy.
  • Anthracyclines: Participants must have had a lifetime exposure of <400 milligrams per square meter (mg/m^2) of doxorubicin equivalents of anthracyclines.
  • a) Adequate renal function defined as: Estimated glomerular filtration rate (eGFR) using the Schwartz formula, OR radioisotope glomerular filtration rate (GFR)≥70 mL/min/1.73 m^2, OR a normal serum creatinine based on age and sex.
  • Adequate liver function defined as: Direct bilirubin ≤1.5 times the upper limit of normal (ULN) for age AND ALT ≤5 times the ULN for age.
  • No clinical, radiological or laboratory evidence of pancreatitis, including:
  • Serum lipase must be <2 times the ULN, AND
  • Serum amylase must be <2 times the ULN.
  • Adequate cardiac function defined as shortening fraction ≥27% by echocardiogram (ECHO) OR left ventricular ejection fraction of ≥50% by ECHO or multigated acquisition scan (MUGA).
  • Normal QT interval with Fridericia correction method (QTcF) on screening electrocardiogram (ECG), defined as QTcF of ≤450 milliseconds (ms).

Who cannot join

  • A history or current diagnosis of Burkitt leukemia/lymphoma or mature B-cell leukemia.
  • A history or current diagnosis of chronic myeloid leukemia (CML).
  • Diagnosis of ALL, MPAL, or Ph-like ALL with targetable kinase-activating lesions after treatment with cytotoxic therapy for another cancer.
  • Diagnosis of another concurrent primary malignancy.
  • Clinically significant cardiovascular disease, including but not limited to:
  • Any history of myocardial infarction (MI) or unstable angina.
Show all 22Show fewer
  • History of or presence of heart block, and/or clinically significant ventricular or atrial arrhythmias.
  • Uncontrolled hypertension, defined as persistent elevation of systolic and/or diastolic blood pressures to ≥95th percentile based on age, sex, and height percentiles despite appropriate antihypertensive management.
  • Current systemic use of drug(s) that are known to have a risk of causing prolonged corrected QT interval (QTc) or torsades de pointes unless drug(s) can be changed to acceptable alternatives (ie, an alternate class of agents that do not affect the cardiac conduction system) or the participants can safely discontinue the drug(s).
  • Uncontrolled hypertriglyceridemia (triglycerides ≥450 milligrams per deciliter (mg/dL)).
  • Current systemic use of any medications or herbal supplements that are known to be strong inhibitors or strong inducers of cytochrome P450 3A (CYP3A) within 7 days before the first dose of study drug.
  • Previous treatment with ponatinib.
  • Planned non-protocol chemotherapy, radiation therapy, another investigational agent, or immunotherapy while participant is on study treatment.
  • Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption of ponatinib.
  • Participants with deoxyribonucleic acid (DNA) fragility syndromes, such as Fanconi anemia and Bloom syndrome.
  • Participants with Down syndrome.
  • Participants with uncontrolled systemic infection, or known laboratory and/or clinical evidence of active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
  • Participants with pre-existing significant CNS pathology, including history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder, or autoimmune disease with CNS involvement, are not eligible.
  • Participants with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. (Participants with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits and causative factor(s) have resolved).
  • Uncontrolled seizure disorder. (Participants with seizure disorders that do not require antiepileptic drugs or are well controlled with stable doses of antiepileptic drugs are eligible).
  • History of severe coagulopathy or cardiovascular or peripheral vascular events.
  • Treatment with live attenuated vaccinations within 30 days prior to initiation of study treatment regimen.

Trial locations and contacts

64 sites in 15 countries.

64 sites in 15 countries

United States13 sites

  • Ann and Robert H Lurie Childrens Hospital of Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center - PIN

    Cincinnati, Ohio, 45229

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Childrens Medical Center Research Institute at UT Southwestern

    Dallas, Texas, 75235-9063

  • Riley Hospital For Children

    Indianapolis, Indiana, 46202-5128

  • Children's Mercy Hospital and Clinica

    Kansas City, Missouri, 64108

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • St Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Rady Childrens Hospital San Diego - PIN

    San Diego, California, 92123

  • UCSF Medical Comprehensive Cancer

    San Francisco, California, 94143-3010

  • Alfred I Dupont Hospital For Children

    Wilmington, Delaware, 19803

Other trials in United States

China11 sites

  • West China Second University Hospital, Sichuan Univesity

    Chengdu, 610041

  • Children's Hospital of Chongqing Medical University

    Chongqing, 400014

  • The Affiliated Hospital of Guizhou Medical University

    Guiyang, 550004

  • The Second Hospital of Anhui Medical University

    Hefei, 230601

  • Qilu Hospital of Shandong University

    Jinan, 250012

  • Children's Hospital of Shanghai

    Shanghai, 200040

  • Shanghai Childrens Medical Center

    Shanghai, 200127

  • Children's Hospital of Soochow University

    Suzhou, 215025

  • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

    Tianjin, 300020

  • Union Hospital Tongji Medical College Huazhong University of Science and Technology

    Wuhan, 430022

  • Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

    Wuhan, 430030

Other trials in China

Brazil7 sites

  • Fundacao Pio XII Hospital de Cancer de Barretos

    Barretos, São Paulo, 14784-400

  • Rua Ramiro Barcelos, 2350

    Curitiba, Paraná, 81520-060

  • Irmandade Da Santa Casa de Misericordia de Porto Alegre

    Porto Alegre, Rio Grande Du Sul, 90020-090

  • Hospital de Clinicas de Porto Alegre (HCPA) - PPDS

    Porto Alegre, Rio Grande Du Sul, 90035-903

  • Hospital Das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP

    Ribeirão Preto, 14051-140

  • Graacc Grupo de Apoio Ao Adolescente E A Crianca Com Cancer

    São Paulo, 04039-001

  • Hospital Santa Marcelina

    São Paulo, 08270-070

Other trials in Brazil

France4 sites

  • Assistance Publique Hopitaux de Marseille

    Marseille, 13385

  • Hopital Robert Debre

    Paris, 75019

  • Hopital Sud

    Rennes, Ille-et-Vilaine, 35200

  • Hopital Des Enfants

    Toulouse, 31059

Other trials in France

Italy4 sites

  • Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN

    Genoa, Liguria, 16147

  • Fndazione MBBM (MONZA E BRIANZA PER IL BAMBINO E LA SUA MAMMA) - c/o Centro Maria Letizia Verga

    Monza, Lombardy, 20900

  • IRCCS Ospedale Pediatrico Bambino Gesu - INCIPIT - PIN

    Rome, Lazio, 165

  • Ospedale Infantile Regina Margherita - INCIPIT - PIN

    Turin, Piedmont, 10126

Other trials in Italy

South Korea4 sites

  • Seoul National University Hospital

    Seoul, 3080

  • Severance Hospital Yonsei University Health System

    Seoul, 3722

  • Asan Medical Center - PPDS

    Seoul, 5505

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul, 6591

Other trials in South Korea

Australia3 sites

  • Perth Childrens Hospital

    Nedlands, Western Australia, 6009

  • Royal Children's Hospital Melbourne - PIN

    Parkville, Victoria, 3052

  • Queensland Childrens Hospital

    South Brisbane, Queensland, 4101

Other trials in Australia

Mexico3 sites

  • Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca

    Guadalajara, 44340

  • Instituto Nacional de Pediatria

    Mexico City, 4530

  • Hospital Universitario Dr. Jose Eleuterio Gonzalez

    Monterrey, Nuevo León, 64460

Other trials in Mexico

Spain3 sites

  • Hospital Universitario Vall d'Hebron - PPDS

    Barcelona, 8035

  • Hospital Infantil Universitario Nino Jesus - PIN

    Madrid, 28009

  • Hospital Universitario Virgen del Rocio - PPDS

    Seville, 41013

Other trials in Spain

United Kingdom3 sites

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge, CB2 0QQ

  • Royal Hospital for Children (Glasgow) - PPDS - PIN

    Glasgow, G3 8SJ

  • Royal Marsden Hospital - Surrey

    Surrey Quays, Sutton, SM2 5PT

Other trials in United Kingdom

Argentina2 sites

  • Hospital Italiano de Buenos Aires

    Buenos Aires, C1199ABB

  • Hospital Universitario Austral

    Pilar, Buenos Aires, B1629AHJ

Other trials in Argentina

Czechia2 sites

  • Fakultni nemocnice Brno

    Brno, 61300

  • Fakultni nemocnice v Motole

    Prague, 15006

Other trials in Czechia

Poland2 sites

  • Uniwersytecki Szpital Dzieciecy

    Krakow, 30-663

  • SPSK Nr 1 im. Prof.Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego

    Zabrze, 41-800

Other trials in Poland

Portugal2 sites

  • Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.

    Lisbon, Lisbon District, 1099-023

  • Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS

    Porto, 4200-072

Other trials in Portugal

Netherlands1 site

  • Princess Maxima Center for Pediatric Oncology - PIN

    Utrecht, 3584 CS

Other trials in Netherlands

About this study

Official title: A Pivotal Phase 1/2, Single-Arm, Open-label Study to Evaluate the Safety and Efficacy of Ponatinib With Chemotherapy in Pediatric Patients With Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) Who Have Relapsed or Are Resistant or Intolerant to a Prior Tyrosine Kinase Inhibitor-Containing Therapy, or Who Have the T315I Mutation

This study is about an anticancer drug called ponatinib which is a tyrosine kinase inhibitor given with chemotherapy to children, teenagers, and young adults up to 21 years of age with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia who have relapsed or are resistant to other treatment.

The main aims of this study are to confirm the highest dose of ponatinib tablets and minitablet capsules that can be given to participants with acceptable side effects, and to evaluate if participant's leukemia achieves remission.

Participants will take ponatinib tablets with chemotherapy. For participants who cannot swallow tablets or who are receiving less than a 10 milligrams (mg) dose, a capsule with small ponatinib minitablets inside will be provided. Participants will take ponatinib for 10 weeks in combination with chemotherapy (reinduction and consolidation blocks) and will be followed up for at least 3 years.

Read the detailed description

The drug being tested in this study is called ponatinib. Ponatinib is being tested to treat pediatric population who have Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), Ph+ mixed phenotype acute leukemia (Ph+ MPAL), or Philadelphia chromosome-like ALL who have relapsed or are resistant or intolerant to a prior tyrosine kinase inhibitor (TKI)-containing therapy, or who have the T315I mutation.

The study will enroll approximately 68 participants. Participants will be assigned to a treatment group either in phase 1 or phase 2. Participants unable to swallow the ponatinib tablets or who are receiving less than a 10 mg dose will receive the age-appropriate formulation, capsule with ponatinib minitablets inside:

  • Ponatinib + Chemotherapy

All participants will be asked to take ponatinib once daily. In phase 1 ponatinib will be administered in combination with a chemotherapy backbone to determine the recommended phase 2 dose (RP2D) of ponatinib. In both phase 1 and phase 2, treatment consists of two 35-day blocks of therapy (reinduction block and consolidation block). Each block will include 29 days of treatment of daily ponatinib and a chemotherapy backbone regimen followed by a rest period from chemotherapy for a minimum of 6 days consisting of daily ponatinib only.

This is a multi-center trial and will be conducted worldwide. The overall time to participate in this study is 6.5 years. Participants will make multiple visits to the clinic, and may be contacted by telephone in at least 36 months of follow-up after treatment.

Being tested
Ponatinib, Chemotherapy Agents
Keywords
Drug Therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PonatinibDrug

    Ponatinib tablets.

  • Chemotherapy AgentsDrug

    Chemotherapy agents for reinduction include vincristine, dexamethasone, polyethylene glycol (PEG)-asparaginase (Erwinia asparaginase when PEG-asparaginase is not available), daunorubicin. Agents for intrathecal (IT) chemotherapy, central nervous system (CNS)-1/2: IT methotrexate chemotherapy, or CNS-3: triple intrathecal (ITT) methotrexate, hydrocortisone, cytarabine. Chemotherapy agents for consolidation include dexamethasone, vincristine, methotrexate, PEG-asparaginase (Erwinia asparaginase when PEG-asparaginase is not available), cyclophosphamide, etoposide, CNS-1/2: IT methotrexate chemotherapy, CNS-3: ITT chemotherapy methotrexate, hydrocortisone, cytarabine. The doses for chemotherapy agents for reinduction will be given as per standard of care.

Study groups in NCT04501614
Study groupRoleWhat they receive
PonatinibExperimentalPonatinib tablets, based on weight, in combination with chemotherapy backbone, orally, once daily in both reinduction block and consolidation block (35 days each including 29 days of treatment followed by rest period from chemotherapy for a minimum of 6 days consisting of daily ponatinib only) in Phase 1 to determine RP2D. In Phase 2 participants will receive ponatinib at RP2D in combination with chemotherapy backbone.
Receives: Drug: Ponatinib; Drug: Chemotherapy Agents

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1: Recommended Phase 2 Dose (RP2D) of Ponatinib in Combination With Chemotherapy

    The RP2D is the maximum tolerated dose (MTD) or less.

    Measured: Up to Day 35 in Phase 1

  2. Phase 2: Percentage of Participants With Complete Remission (CR) at the End of the Reinduction Block

    CR was defined as no circulating blasts and less than (<)5 percent (%) blasts in the bone marrow (BM); normal maturation of all cellular components in the bone marrow; no extramedullary disease; absolute neutrophil count (ANC) greater than (>)1000 cells/microliter (μL) (or >1.0 × 10^9 cells/liter [L]); Platelets >100,000/μL (or >100 × 10^9 platelets/L).

    Measured: Up to Day 35 in Phase 2

Secondary outcomes (14)

  1. Phase 1: Number of Participants With CR at the End of Reinduction Block

    CR was defined as no circulating blasts and <5% blasts in the BM; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC >1000 cells/μL (or >1.0 × 10^9 cells/L); Platelets >100,000/μL (or >100 × 10^9 platelets/L).

    Measured: Day 35 in Phase 1

  2. Phase 2: Percentage of Ph+ ALL Participants Who Achieved CR at the End of Consolidation Block

    CR was defined as no circulating blasts and <5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC >1000 cells/μL (or >1.0 × 10^9 cells/L); Platelets >100,000 platelets/μL (or >100 × 10^9 platelets/L).

    Measured: Day 70 in Phase 2

  3. Phase 2: Percentage of Ph+ ALL Participants With Negative Minimal Residual Disease (MRD) Among Those Who Achieved CR

    MRD negative rate is the percentage of participants who achieve MRD negative status by evaluation of bone marrow aspirate at <0.01% threshold.

    Measured: Up to Day 70 (end of consolidation block) in Phase 2

  4. Phase 2: Percentage of Participants Who Relapsed or Progressed Following Reinduction and Consolidation

    Measured: Up to 3 years of follow-up in Phase 2

  5. Phase 2: Event-free Survival (EFS)

    EFS was defined as time from date of enrollment until death due to any cause; refractory to treatment (defined as failure to achieve CR by end of the consolidation block) or relapse from CR. CR was defined as no circulating blasts and <5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC >1000 cells/μL (or >1.0 × 10^9 cells/L); Platelets >100,000 platelets/μL (or >100 × 10^9 platelets/L).

    Measured: Up to 3 years of follow-up in Phase 2

  6. Phase 2: Progression-free Survival (PFS)

    PFS was defined as time from date of enrolment until death related to disease under study; disease progression (clinical deterioration associated with disease process, including evidence of increasing blasts in the bone marrow from baseline and/or evidence of new organ involvement) or relapse from CR. CR was defined as no circulating blasts and <5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC >1000 cells/μL (or >1.0 × 10^9 cells/L); Platelets >100,000 platelets/μL (or >100 × 10^9 platelets/L).

    Measured: Up to 3 years of follow-up in Phase 2

  7. Phase 2: Overall Survival (OS)

    OS was defined as time from first dose of ponatinib until death due to any cause.

    Measured: Up to 3 years of follow-up in Phase 2

  8. Phase 2: Duration of Response (DOR)

    DOR was defined as the interval between the first assessment at which the criteria for CR are met until the time at which relapse from CR occurs. CR was defined as no circulating blasts and <5% blasts in the bone marrow; normal maturation of all cellular components in the bone marrow; no extramedullary disease; ANC >1000 cells/μL (or >1.0 × 10^9 cells/L); Platelets >100,000 platelets/μL (or >100 × 10^9 platelets /L).

    Measured: Up to 3 years of follow-up in Phase 2

  9. Phase 2: Percentage of Participants Who Underwent Hematopoietic Stem Cell Transplantation (HSCT)

    Measured: Up to 3 years of follow-up in Phase 2

  10. Phase 1: Cmax: Maximum Observed Plasma Concentration for Ponatinib

    Measured: Predose and at multiple timepoints post-dose up to 24 hours on Days 1 and 22 in Phase 1

  11. Phase 1: Tmax: Time of First Occurrence of Cmax for Ponatinib

    Measured: Predose and at multiple timepoints post-dose up to 24 hours on Days 1 and 22 in Phase 1

  12. Phase 1: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ponatinib

    Measured: Predose and at multiple timepoints post-dose up to 24 hours on Days 1 and 22 in Phase 1

  13. Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Venous Thrombotic/Embolic Events (VTEs), and Adverse Events of Special Interest (AESIs)

    An adverse event (AE) is defined as any untoward medical occurrence in clinical study participant, temporally associated with use of study intervention, whether or not occurrence was considered related to the study intervention including any unfavorable \& unintended sign (e.g., clinically significant abnormal laboratory finding), symptom/disease. TEAE: any AE that occurs after administration of first dose of any study drug \& through 30 days after last dose of any study drug. Serious TEAE:AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization/prolongation of existing hospitalization, resulted in persistent/significant disability or incapacity, was congenital anomaly/birth defect, was medically important event. AESI: Protocol-defined AEs resulting in compromise of organ function or other significant consequences. VTEs were identified as AESIs for ponatinib and included arterial, VTEs that meet criteria for serious TEAEs.

    Measured: Up to 34.8 months in Phase 1

  14. Phase 2: Number of Participants With TEAEs, Serious TEAEs, VTEs, and AESIs

    An AE is defined as any untoward medical occurrence in clinical study participant, temporally associated with use of study intervention, whether or not occurrence was considered related to the study intervention including any unfavorable \& unintended sign (e.g., clinically significant abnormal laboratory finding), symptom/disease. TEAE: any AE that occurs after administration of first dose of any study drug \& through 30 days after last dose of any study drug. Serious TEAE:AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization/prolongation of existing hospitalization, resulted in persistent/significant disability or incapacity, was congenital anomaly/birth defect, was medically important event. AESI: Protocol-defined AEs resulting in compromise of organ function or other significant consequences. VTEs were identified as AESIs for ponatinib and included arterial, VTEs that meet criteria for serious TEAEs.

    Measured: Up to 30 days after last dose of ponatinib in Phase 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2020
  2. Study start24 Feb 2021
  3. Primary completion19 Dec 2023
  4. Study completion19 Jul 2024

Why it stopped: Phase 1 enrollment was terminated due to dose-limiting toxicities, thus the study was terminated by Sponsor.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04501614
Sponsor's protocol ID
Ponatinib-1501
Other IDs
2019-002549-39, U1111-1225-0394, 2019
Status last verified
Sep 2025
First submitted
4 Aug 2020
Last updated
2 Oct 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be reidentified (due to the limited number of study participants/study sites).

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ponatinib and Chemotherapy Agents in people with Pediatric Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ALL) and Ph+ Mixed Phenotype Acute Leukemia (MPAL), run by Takeda at 64 sites in 15 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 28 inclusion and 22 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: stopped early, as of the sponsor's last update on 2 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in United States, China, Brazil, France, Italy and 10 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 15 Jan 2025). 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?

Phase 1: Recommended Phase 2 Dose (RP2D) of Ponatinib in Combination With Chemotherapy (time frame: Up to Day 35 in Phase 1). The study lists 2 primary outcomes in all. 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 NCT04501614.

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 2 Oct 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in