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Hyper-CVAD + ponatinib
- Development stage
- Unknown
- Lead developer
- University of Texas MD Anderson Cancer Center
- Modality
- Nucleic Acid-Directed Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules
- Administration
- Intravenous, Oral
01
Overview
Hyper-CVAD + ponatinib is a combination treatment regimen developed by the M.D. Anderson Cancer Center for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML) in advanced phases. The regimen combines the Hyper-CVAD chemotherapy backbone—consisting of hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Course A) alternating with high-dose methotrexate and cytarabine (Course B)—with ponatinib, a potent third-generation BCR-ABL1 tyrosine kinase inhibitor. Ponatinib is uniquely effective against the T315I 'gatekeeper' mutation, which confers resistance to earlier TKIs like imatinib and dasatinib. This intensive chemo-immunotherapy approach has demonstrated high rates of complete molecular remission and improved long-term survival in Ph+ ALL patients, potentially reducing the necessity for allogeneic stem cell transplantation.
- Other names
- Hyper-CVAD and ponatinibHyper-CVAD plus ponatinibHyper-CVAD-ponatinib
02
Targets
SFK (SRC family kinases)PDGFR (PDGFR family)VEGFR (VEGFR family)FGFR (Fibroblast growth factor receptor)TOP2A (DNA topoisomerase II)DNA polymerase familyABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)DHFR (Dihydrofolate reductase)GR (Glucocorticoid receptor)DNATUBB (Tubulin (alpha and beta subunits))
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