Safety and Efficacy of Ponatinib for Treatment of Pediatric Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors

NCT03934372 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: INCB 84344-1022023-509699-41-002018-004878-99
• Study Type: interventional
• Target: 70
• Locations: 7 countries
• Sites: 23

Brief 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.

Conditions

Blast Phase Chronic Myeloid Leukemia; Acute Lymphocytic Leukemia; Lymphoma; Solid Tumors; Accelerated Phase Chronic Myeloid Leukemia; Acute Myeloid Leukemia; Leukemia; Chronic Phase Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia

Keywords

Leukemia; Solid tumors; Pediatric; Tyrosine kinase inhibitor; lymphomas

Outcome Measures

Primary Outcomes (7)

• 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.

  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).

  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).

  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

  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.

  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 \[PET\]).

  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).

  6 months

Secondary Outcomes (31)

• Phase 1: Number of treatment-emergent adverse events

  6 months

• Phase 1: Tmax of ponatinib

  6 months

• Phase 1: AUCss,0-24 of ponatinib

  6 months

• Phase 1: t½ of ponatinib

  6 months

• Phase 1: CLss/F of ponatinib

  6 months

Study Arms (1)

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.

Drug: Ponatinib

Interventions

Ponatinib DRUG

Ponatinib administered as a tablet or age-appropriate formulation for pediatric participants according to age-based cohort assignment.

Also known as: Iclusig, INCB84344

Ponatinib

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Incyte Biosciences International Sàrl: lead

Study Sites (23)

Ghent University Hospital

Ghent, 09000, Belgium

RECRUITING

Hopital Robert Debre

Paris, 75019, France

RECRUITING

Armand Trousseau Hospital

Paris, 75571, France

RECRUITING

Centre Hospitalier Universitaire de Poitiers

Poitiers, 86021, France

RECRUITING

Chu de Rennes - Hospital Sud

Rennes, 35700, France

COMPLETED

Aou Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

RECRUITING

Asst Degli Spedali Civili Di Brescia

Brescia, 25123, Italy

RECRUITING

Ospedale Pediatrico G. Gaslini

Genova, 16147, Italy

RECRUITING

Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano

Milan, 20133, Italy

RECRUITING

University of Milano Bicocca

Monza, 20900, Italy

RECRUITING

Aorn Santobono Pausilipon

Naples, 80122, Italy

NOT YET RECRUITING

Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo

Pavia, 27100, Italy

RECRUITING

Ospedale Pediatrico Bambino Gesu Irccs

Rome, 00165, Italy

RECRUITING

A.O.U Citta Della Salute E Della Scienza Di Torino Presidio Ospedaliero Infantile Regina Margherita

Torino, 10126, Italy

RECRUITING

Princess Maxima Center For Pediatric Oncology

Utrecht, 03584, Netherlands

RECRUITING

Hospital General Universitario Vall D Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Sant Joan de Deu de Manresa

Barcelona, 08035, Spain

RECRUITING

Hospital Infantil Unversitario Nino Jesus

Madrid, 28009, Spain

RECRUITING

Hospital Universitari I Politecnic La Fe

Valencia, 46026, Spain

RECRUITING

Karolinska University Hospital Solna

Stockholm, 14141, Sweden

RECRUITING

Royal Hospital For Sick Children Yorkhill Glasgow

Glasgow, G514TF, United Kingdom

RECRUITING

Alder Hey Childrens Nhs Foundation Trust

Liverpool, L12 2AP, United Kingdom

RECRUITING

The Royal Marsden Nhs Foundation Trust - Sutton

Sutton, SM2 5PT, United Kingdom

RECRUITING

Related Links

• Safety and Efficacy of Ponatinib for Treatment of Pediatric Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Leukemia, Myeloid, Chronic-Phase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Lymphoma

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Mohammed-El-Amine Bensmaine, MD

  Incyte Biosciences International Sàrl

  STUDY DIRECTOR

Central Study Contacts

Incyte Corporation Call Center (ex-US)

CONTACT

+800 00027423; globalmedinfo@incyte.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2019
• First Posted: May 1, 2019
• Study Start: January 29, 2020
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (9); FR (4); ES (4); SE (1); GB (3); BE (1); NL (1)