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trametinib + dexamethasone + cyclophosphamide + cytarabine
- Development stage
- Phase 2
- Lead developer
- Princess Máxima Center for Pediatric Oncology
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
This combination therapy consists of the small molecule MEK inhibitor trametinib administered in conjunction with a chemotherapy backbone comprising dexamethasone, cyclophosphamide, and cytarabine. It is currently being evaluated by the Princess Maxima Center for Pediatric Oncology in the Phase I/II HEM-iSMART Sub-protocol D trial (NCT05658640). The regimen is specifically designed for pediatric, adolescent, and young adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) whose malignancies harbor alterations in the RAS-RAF-MAPK signaling pathway. Trametinib acts as a highly selective, reversible inhibitor of mitogen-activated protein kinase kinase 1 (MEK1) and 2 (MEK2), effectively blocking the downstream signaling that drives leukemic cell proliferation and survival. The addition of dexamethasone (a glucocorticoid), cyclophosphamide (an alkylating agent), and cytarabine (an antimetabolite) provides a synergistic cytotoxic effect to overcome resistance in heavily pretreated hematological malignancies.
- Other names
- Trametinib + Dexamethasone + Cyclophosphamide + Cytarabine
02
Targets
DNADNA polymerase familyGR (Glucocorticoid receptor)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)
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