Acute Myeloid LeukemiaPhase 1/2NCT03934372
Safety and Efficacy of Ponatinib for Treatment of Pediatric Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors
A Phase 1/2 study testing Ponatinib in people with Acute Myeloid Leukemia and Accelerated Phase Chronic Myeloid Leukemia, run by Incyte Biosciences International Sàrl at 23 sites in 7 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ponatinib in children aged 1 to < 18 years with advanced leukemias, lymphomas, and solid tumors. Read more about this study
- Who is it for?
- Ages 1 year to 17 years
- Conditions the study is for
- Acute Myeloid Leukemia, Accelerated Phase Chronic Myeloid Leukemia, Blast Phase Chronic Myeloid Leukemia
- What is being tested?
- Ponatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 23 sitesin 7 countries
- Study dates
- 29 Jan 2020to 1 Feb 2028
- Phase
- Phase 1/2
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 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Histologically or cytologically confirmed diagnosis of the following malignancies:
- Phase 1: CP-CML, BP-CML, AP-CML ALL. AML. Other leukemias. Lymphoma. Any other tumors, including tumors of the CNS, for which standard therapy is not available or is not indicated.
- Phase 2, Group A with CP-CML: CP-CML at the time of study entry and must be resistant to or intolerant of at least 1 prior BCR-ABL-targeted TKI therapy or be in "warning" response status or have the T315I kinase domain mutation.
- Must have 1 bone marrow aspirate with documentation of BCR-ABL translocation by conventional cytogenetics, metaphase FISH, or q-PCR performed within 42 days before the first dose of ponatinib.
- Phase 2, Group B with other leukemias or solid tumors: ALL. AML. Other leukemias. Lymphoma. Any other tumors, including tumors of the CNS, with mutations of RET, FLT3, KIT, FGFR, PDGFR, TIE2, VEGFR, or any other mutations where ponatinib may have biological activity (eg, EPH receptors and SRC families of kinases) as assessed on fresh or archived tumor tissue.
- Participants with solid tumors or with lymphoma must have measurable disease by CT or MRI based on RECIST v1.1 or the Lugano lymphoma guidelines as determined by site radiology.
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- Prior therapies as follows:
- Phase 1: Participants with CML who are resistant to or intolerant of (as defined Appendix F) to at least 1 prior BCR-ABL-targeted TKI therapy.
- Participants with ALL who have progressed on or after all available or indicated therapies, which may have included 1 prior BCR-ABL-targeted TKI therapy.
- Participants with AML or other leukemias who have progressed on or after at least 1 prior induction attempt (for France only) or for whom no effective standard therapy is available or indicated (other countries).
- Participants with solid tumors (including tumors of the CNS) or lymphomas who have progressed despite standard therapy or for whom no effective standard therapy is available or indicated.
- Phase 2, Group A with CP-CML: Participants who are resistant to or intolerant of at least 1 prior BCR-ABL-targeted TKI therapy.
- Phase 2, Group B with other leukemias or solid tumors: Participants with ALL who have progressed on or after all available or indicated therapies, which must have included 1 prior BCR-ABL-targeted TKI therapy.
- Participants with AML or other leukemias who have progressed on or after at least 1 prior induction attempt (for France only) or for whom no effective standard therapy is available or indicated (other countries).
- Participants with solid tumors (including tumors of the CNS) or lymphomas who progressed despite standard therapy or for whom no effective standard therapy is available or indicated.
- Karnofsky performance status ≥ 40% for participants ≥ 16 years old or Lansky Play Scale ≥ 40% for pediatric participants < 16 years old.
- Participants must have recovered to < Grade 2 per the NCI CTCAE v5.0 or to baseline from any non-hematologic toxicities (except alopecia) due to previous therapy.
- Willingness to avoid pregnancy or fathering children.
Who cannot join
- Prior therapies:
- Participants with BP-CML, ALL, or AML who have received any of the following: Corticosteroids or hydroxyurea within 24 hours before the first dose of ponatinib.
- Vincristine within 7 days before the first dose of ponatinib. Other chemotherapy (excluding intrathecal chemotherapy) within 14 days before the first dose of ponatinib.
- Participants (except the BP-CML, ALL, and AML participants described above) who: Have had cytotoxic chemotherapy within 21 days (or 42 days for nitrosoureas or mitomycin C) before the first dose of ponatinib.
- Prior radiation therapy or radio-isotope therapy within 6 weeks before the first dose of ponatinib except local radiotherapy for palliative indication within 14 days before the first dose of ponatinib.
- Autologous or allogeneic stem cell transplant < 3 months before the first dose of ponatinib.
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- Major surgery within 14 days before the first dose of ponatinib. Inadequate recovery and/or complications from a major surgery before starting therapy.
- Prior treatment with any of the following:
- Immunosuppressive therapy (including post stem cell transplant regimens) within 14 days before the first dose of ponatinib.
- Any targeted cancer therapy (including TKIs) within 7 days before the first dose of ponatinib.
- Any other investigational anticancer agents within 30 days or 5 half-lives, whichever is longer, before randomization.
- Any monoclonal antibody-directed anticancer therapy within 5 half-lives of the first dose of ponatinib.
- Any chimeric antigen receptor therapy within 28 days before the first dose of ponatinib
- Ponatinib
- Protocol-defined lab Values
- Significant concurrent, uncontrolled medical condition, including but not limited to the following:
- Pancreatic: clinical, radiological, or laboratory evidence of pancreatitis.
- Cardiac:
- SF < 27% by ECHO, OR EF < 50% by MUGA.
- Abnormal QTcF on screening ECG, defined as QTcF of ≥ 450 ms.
- Clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute MI within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV CHF (see Appendix P), and arrhythmia requiring therapy unless approved by the medical monitor/sponsor.
- Uncontrolled hypertension.
- Currently taking drug(s) that are known to have a risk of causing prolonged QTc or TdP unless the drug(s) can be changed to acceptable alternatives (ie, an alternate class of agents that do not affect the cardiac conduction system), or the participant can safely discontinue the drug(s).
- Cerebral:
- Participants with solid tumors with intracranial metastasis OR participants with active CNS leukemia (ie, CNS-2 status [< 5/μL WBCs and cytospin positive for blasts, or ≥ 5 /μL WBCs but negative by Steinherz/Bleyer algorithm (equation used for traumatic lumbar punctures), disseminated leptomeningeal disease, or CNS chloroma.
- 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.
- History of cerebrovascular ischemia/hemorrhage with residual deficits.
- Note: Participants with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved clinically according to Inclusion Criterion 6.
- Uncontrolled seizure disorder.
- Coagulation:
- Significant bleeding disorder or thrombophilia unrelated to the underlying malignancy indication for study participation.
- Gastrointestinal:
- Gastrointestinal disorders, such as malabsorption syndrome or any other illness that could affect oral absorption.
- Genetic:
- Participants with DNA fragility syndromes, such as Fanconi anemia and Bloom syndrome.
- Participants with Down syndrome.
- Participants with any active ≥ Grade 2 graft versus host disease.
- Chronic or current active uncontrolled infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
- Active HBV or HCV infection that requires treatment or at risk for HBV reactivation. Hepatitis B virus DNA and HCV RNA must be undetectable upon testing. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive.
- Known HIV infection.
- Current use of prohibited medication (see Section 6.7.2).
- Known hypersensitivity or severe reaction to ponatinib or excipients of ponatinib.
- Receipt of live (including attenuated) vaccines or anticipation of need for such vaccines during the study.
- Inability or unlikeliness to comply with the dose schedule and study evaluations, in the opinion of the investigator.
- Females who are pregnant or lactating.
- Other exclusions may apply.
Trial locations and contacts
23 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
23 sites in 7 countries
Italy9 sites, 9 recruiting
- Recruiting
Aou Policlinico S. Orsola-Malpighi
Bologna, 40138
- Recruiting
Asst Degli Spedali Civili Di Brescia
Brescia, 25123
- Recruiting
Ospedale Pediatrico G. Gaslini
Genova, 16147
- Recruiting
Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano
Milan, 20133
- Recruiting
University of Milano Bicocca
Monza, 20900
- Recruiting
Aorn Santobono Pausilipon
Naples, 80122
- Recruiting
Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
Pavia, 27100
- Recruiting
Ospedale Pediatrico Bambino Gesu Irccs
Rome, 00165
- Recruiting
A.O.U Citta Della Salute E Della Scienza Di Torino Presidio Ospedaliero Infantile Regina Margherita
Torino, 10126
France4 sites, 3 recruiting
- Recruiting
Hopital Robert Debre
Paris, 75019
- Recruiting
Armand Trousseau Hospital
Paris, 75571
- Recruiting
Centre Hospitalier Universitaire de Poitiers
Poitiers, 86021
- Completed
Chu de Rennes - Hospital Sud
Rennes, 35700
Spain4 sites, 4 recruiting
- Recruiting
Hospital General Universitario Vall D Hebron
Barcelona, 08035
- Recruiting
Hospital Sant Joan de Deu de Manresa
Barcelona, 08035
- Recruiting
Hospital Infantil Unversitario Nino Jesus
Madrid, 28009
- Recruiting
Hospital Universitari I Politecnic La Fe
Valencia, 46026
United Kingdom3 sites, 3 recruiting
- Recruiting
Royal Hospital For Sick Children Yorkhill Glasgow
Glasgow, G514TF
- Recruiting
Alder Hey Childrens Nhs Foundation Trust
Liverpool, L12 2AP
- Recruiting
The Royal Marsden Nhs Foundation Trust - Sutton
Sutton, SM2 5PT
Netherlands1 site, 1 recruiting
- Recruiting
Princess Maxima Center For Pediatric Oncology
Utrecht, 03584
Sweden1 site, 1 recruiting
- Recruiting
Karolinska University Hospital Solna
Stockholm, 14141
About this study
Official title: An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy of Ponatinib for the Treatment of Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors in Pediatric Participants
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ponatinib in children aged 1 to < 18 years with advanced leukemias, lymphomas, and solid tumors.
- Conditions
- Acute Myeloid Leukemia, Accelerated Phase Chronic Myeloid Leukemia, Blast Phase Chronic Myeloid Leukemia, Chronic Phase Chronic Myeloid Leukemia, Acute Lymphoblastic Leukemia, Acute Lymphocytic Leukemia
- Being tested
- Ponatinib
- Keywords
- Leukemia, Solid tumors, Pediatric, Tyrosine kinase inhibitor, lymphomas
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Myeloid, Accelerated Phase, Blast Crisis, Leukemia, Myeloid, Chronic-Phase, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PonatinibDrug
Also called Iclusig, INCB84344
Ponatinib administered as a tablet or age-appropriate formulation for pediatric participants according to age-based cohort assignment.
| Study group | Role | What they receive |
|---|---|---|
| Ponatinib | Experimental | Phase 1: Ponatinib administered according to age-based cohort doses and formulations to determine the maximum tolerated dose and recommended Phase 2 dose. Phase 2: Ponatinib administered at the recommended Phase 2 dose. Receives: Drug: Ponatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of dose-limiting toxicities
Defined as the occurrence of any protocol-defined toxicities occurring after dosing and up to and including Day 28, except those toxicities with a clear alternative explanation.
Measured: 28 days
Phase 2: Efficacy of ponatinib assessed by major cytogenetic response (MCyR) in participants with chronic-phase chronic myeloid leukemia (CP-CML)
Defined as complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) as assessed by conventional cytogenetics or fluorescence in situ hybridization (FISH).
Measured: 12 months
Phase 2: Efficacy of ponatinib assessed by major hematologic response (MaHR) or major molecular response (MMR) in participants with BCR-ABL-positive leukemias
Assessed by polymerase chain reaction (PCR).
Measured: 3 months
Phase 2: Efficacy of ponatinib assessed by complete response (CR) in participants with leukemias other than BCR-ABL-positive leukemias to determine the efficacy of ponatinib
Measured: 6 months
Phase 2: Efficacy of ponatinib assessed by incomplete complete response (iCR) in participants with leukemias other than BCR-ABL-positive leukemias
Assessed by conventional cytogenetics, FISH, or PCR.
Measured: 6 months
Phase 2: Efficacy of ponatinib assessed by CR in participants with lymphoma
According to Lugano criteria based on computed tomography (CT) or magnetic resonance imaging (MRI) (or positron emission tomography [PET]).
Measured: 6 months
Phase 2: Efficacy of ponatinib assessed by overall response rate in participants with solid tumors
Defined as the percentage of participants having CR or PR, as determined by investigator assessment of radiographic disease per tumors per RANO for central nervous system (CNS) tumors or Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for other solid tumors based on CT or MRI (or PET).
Measured: 6 months
Secondary outcomes (31)
Phase 1: Number of treatment-emergent adverse events
Measured: 6 months
Phase 1: Tmax of ponatinib
Time to maximum concentration.
Measured: 6 months
Phase 1: AUCss,0-24 of ponatinib
Area under the steady-state plasma or serum concentration-time curve from Hour 0 to 24.
Measured: 6 months
Phase 1: t½ of ponatinib
Apparent terminal-phase disposition half-life.
Measured: 6 months
Phase 1: CLss/F of ponatinib
Apparent oral dose clearance at steady state.
Measured: 6 months
Phase 1: Vz/F of ponatinib
Apparent oral dose volume of distribution.
Measured: 6 months
Phase 1: MCyR in participants with BCR-ABL-positive leukemias
Defined as CCyR or PCyR as assessed by conventional cytogenetics or FISH.
Measured: 3 months
Phase 1: MMR in participants with BCR-ABL-positive leukemias
Assessed by quantitative PCR (q-PCR).
Measured: 3 months
Phase 1 and Phase 2: Complete hematologic response (CHR) in participants with CP-CML
Measured: 6 months
Phase 1 and Phase 2: CCyR in participants with CP-CML
Measured: 12 months
Phase 1 and Phase 2: MMR in participants with CP-CML
Measured: 12 months
Phase 1 and Phase 2: Time to response (TTR) in participants with CP-CML
Defined as the interval from the date of the first dose of study treatment to first response.
Measured: 6 months
Phase 1 and Phase 2: Duration of response (DOR) in participants with CP-CML
Defined as the interval between the first assessment at which the criteria for response are met until the criteria for progression are met.
Measured: 6 months
Phase 1 and Phase 2: Progression-free survival (PFS) in participants with CP-CML
Defined as the interval from the date of the first dose of study treatment until the date of progression of disease or the date of death from any cause, whichever is earlier.
Measured: 6 months
Phase 1 and Phase 2: Overall survival (OS) in participants with CP-CML
Defined as the interval from the date of the first dose of study treatment until death from any cause.
Measured: 6 months
Phase 1: CR in participants with leukemias other than BCR-ABL-positive leukemia or CP-CML.
Measured: 6 months
Phase 1: CRi in participants with leukemias other than BCR-ABL-positive leukemia or CP-CML
Assessed by conventional cytogenetics, FISH, or q-PCR.
Measured: 6 months
Phase 1: CR in participants with lymphoma
According to Lugano criteria based on CT or MRI (or PET).
Measured: 6 months
Phase 1: Overall response rate in participants with solid tumors
Defined as the percentage of participants having CR or PR, as determined by investigator assessment of radiographic disease per tumors per RANO for CNS tumors or RECIST v1.1 for other solid tumors based on CT or MRI (or PET).
Measured: 6 months
Phase 2: Anticancer activity of ponatinib assessed by MaHR or MMR in participants with BCR-ABL-positive leukemias (AP-CML, BP-CML or Ph+ALL)
Measured: 3 months
Phase 2: Anticancer activity of ponatinib assessed by CR in participants with leukemias other than BCR-ABL-positive leukemias
Measured: 6 months
Phase 2: Anticancer activity of ponatinib assessed by CRi in participants with leukemias other than BCR-ABL-positive leukemias.
Assessed by conventional cytogenetics, FISH, or PCR.
Measured: 6 months
Phase 2: Anticancer activity of ponatinib assessed by CR in participants with lymphoma
According to Lugano criteria based on CT or MRI (or PET).
Measured: 6 months
Phase 2: Anticancer activity of ponatinib assessed by overall response rate in participants with solid tumors
Defined as the percentage of participants having CR or PR, as determined by investigator assessment of radiographic disease per tumors per RANO for CNS tumors or RECIST v1.1 for other solid tumors based on CT or MRI (or PET).
Measured: 6 months
Phase 2: OS in participants with solid tumors
Defined as the interval from the date of the first dose of study treatment until death from any cause.
Measured: 6 months
Phase 2: DOR in participants with solid tumors
Defined as the interval between the first assessment at which the criteria for response are met until the criteria for progression are met.
Measured: 6 months
Phase 2: PFS in participants with solid tumors
Defined as the interval from the date of the first dose of study treatment until the date of progression of disease or the date of death from any cause, whichever is earlier.
Measured: 6 months
Phase 2: Number of treatment-emergent adverse events
Measured: 6 months
Phase 2: Clearance of pediatric-friendly formulation of ponatinib
Measured: 6 months
Phase 2: Volume of distribution of pediatric-friendly formulation of ponatinib
Measured: 6 months
Phase 2: AUC of pediatric-friendly formulation of ponatinib
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2019
- Study start29 Jan 2020
- Primary completion1 Feb 2028 (estimated)
- Study completion1 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Incyte Biosciences International Sàrl
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mohammed-El-Amine Bensmaine, MD, Study director, Incyte Biosciences International Sàrl
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03934372
- Sponsor's protocol ID
- INCB 84344-102
- Other IDs
- 2023-509699-41-00, 2018-004878-99, 2018, 2023
- Status last verified
- Oct 2026
- First submitted
- 29 Apr 2019
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No