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

Required: BCR ABL fusion

documentation of BCR-ABL translocation by conventional cytogenetics, metaphase FISH, or q-PCR

Allowed: ABL1 T315I

have the T315I kinase domain mutation

Allowed: RET mutation

mutations of RET ... as assessed on fresh or archived tumor tissue

Allowed: FLT3 mutation

mutations of FLT3 ... as assessed on fresh or archived tumor tissue

Allowed: KIT mutation

mutations of KIT ... as assessed on fresh or archived tumor tissue

Allowed: FGFR1 mutation

mutations of FGFR ... as assessed on fresh or archived tumor tissue

Allowed: PDGFRA mutation

mutations of PDGFR ... as assessed on fresh or archived tumor tissue

Allowed: TIE2 mutation

mutations of TIE2 ... as assessed on fresh or archived tumor tissue

Allowed: VEGFR1 mutation

mutations of VEGFR ... as assessed on fresh or archived tumor tissue

Must have received: BCR-ABL inhibitor — CML, ALL

resistant to or intolerant of at least 1 prior BCR-ABL-targeted TKI therapy

Must have received: induction chemotherapy — AML, other leukemias

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)

Must have received: standard therapy — solid tumors, lymphoma

progressed despite standard therapy or for whom no effective standard therapy is available or indicated

Cannot have received: ponatinib (ponatinib)

Ponatinib

Cannot have received: immunosuppressive therapy

Immunosuppressive therapy (including post stem cell transplant regimens) within 14 days before the first dose of ponatinib

Cannot have received: targeted cancer therapy

Any targeted cancer therapy (including TKIs) within 7 days before the first dose of ponatinib

Cannot have received: investigational anticancer agents

Any other investigational anticancer agents within 30 days or 5 half-lives, whichever is longer, before randomization

Cannot have received: monoclonal antibody-directed anticancer therapy

Any monoclonal antibody-directed anticancer therapy within 5 half-lives of the first dose of ponatinib

Cannot have received: chimeric antigen receptor therapy

Any chimeric antigen receptor therapy within 28 days before the first dose of ponatinib

Cannot have received: autologous or allogeneic stem cell transplant

Autologous or allogeneic stem cell transplant < 3 months before the first dose of ponatinib

Cannot have received: cytotoxic chemotherapy

cytotoxic chemotherapy within 21 days (or 42 days for nitrosoureas or mitomycin C) before the first dose of ponatinib

Cannot have received: radiation therapy

Exception: local radiotherapy for palliative indication within 14 days 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

Cannot have received: major surgery

Major surgery within 14 days before the first dose of ponatinib