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

Who is this study for? Children aged 1 to < 18 years with advanced leukemias, lymphomas, and solid tumors
What treatments are being studied? Ponatinib
Status: Recruiting
Location: See all (29) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Maximum Age: 17
Healthy Volunteers: No
View:

⁃ 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.

⁃ 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.

⁃ 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.

⁃ 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.

Locations
Other Locations
Belgium
Ghent University Hospital
Recruiting
Ghent
Denmark
The Finsen Centre National Hospital
Not yet recruiting
Copenhagen
France
Armand Trousseau Hospital
Not yet recruiting
Paris
Hopital Robert Debre
Recruiting
Paris
Centre Hospitalier Universitaire de Poitiers
Recruiting
Poitiers
Chu de Rennes - Hospital Sud
Not yet recruiting
Rennes
Germany
Universitaetsklinikum Erlangen - Medizinische Klinik 5
Not yet recruiting
Erlangen
Universitatsklinikum Essen
Not yet recruiting
Essen
Italy
L Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola ? Malpighi
Not yet recruiting
Bologna
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Not yet recruiting
Brescia
Ospedale Pediatrico G. Gaslini
Not yet recruiting
Genova
Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori
Recruiting
Milan
Ospedale San Gerardo - Asst Monza
Not yet recruiting
Monza
University of Milano Bicocca
Recruiting
Monza
Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
Not yet recruiting
Pavia
Ospedale Pediatrico Bambino Gesu Irccs
Recruiting
Rome
Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza
Recruiting
Torino
Netherlands
Princess Maxima Center For Pediatric Oncology
Recruiting
Utrecht
Spain
Hospital Sant Joan de Deu de Manresa
Not yet recruiting
Barcelona
Hospital Nino Jesus
Recruiting
Madrid
Hospital Universitario de La Paz
Completed
Madrid
Hospital Universitari I Politecnic La Fe
Not yet recruiting
Valencia
Sweden
Karolinska Universitetssjukhuset Solna
Not yet recruiting
Solna
Karolinska University Hospital Solna
Recruiting
Stockholm
United Kingdom
University Hospital Birmingham
Not yet recruiting
Birmingham
Royal Hospital For Sick Children Yorkhill Glasgow
Not yet recruiting
Glasgow
Alder Hey Childrens Nhs Foundation Trust
Not yet recruiting
Liverpool
The Royal Marsden NHS Foundation Trust
Not yet recruiting
Sutton
The Royal Marsden Nhs Foundation Trust - Sutton
Recruiting
Sutton
Contact Information
Primary
Incyte Corporation Call Center (ex-US)
globalmedinfo@incyte.com
+800 00027423
Time Frame
Start Date: January 29, 2020
Estimated Completion Date: January 4, 2025
Participants
Target number of participants: 60
Treatments
Experimental: Ponatinib
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.
Sponsors
Leads: Incyte Biosciences International Sàrl

This content was sourced from clinicaltrials.gov

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