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temsirolimus + dexamethasone + mitoxantrone + vincristine + pegaspargase + methotrexate
- Development stage
- Discontinued
- Lead developer
- Children's Oncology Group
- Modality
- Recombinant Proteins and Enzymes, Small Molecules
- Administration
- Intravenous, Oral, Intrathecal
01
Overview
This combination therapy is an intensive re-induction chemotherapy regimen studied by the National Cancer Institute (NCI) and the Children's Oncology Group (COG) for pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). The regimen utilizes a backbone of the UKALL R3 protocol—consisting of dexamethasone, mitoxantrone, vincristine, and pegaspargase—augmented with the mTOR inhibitor temsirolimus. Temsirolimus targets the PI3K/AKT/mTOR signaling pathway, which is frequently dysregulated in lymphoid malignancies, to enhance the cytotoxic effects of the chemotherapy components. A Phase 1 dose-escalation study (ADVL1114) evaluated this combination but found that it resulted in excessive toxicity, including hypertriglyceridemia, mucositis, and sepsis, at all dose levels tested.
- Brand names
- Torisel
- Other names
- Temsirolimus and intensive re-induction therapyUKALL R3 with temsirolimus
02
Targets
DHFR (Dihydrofolate reductase)TOP2A (DNA topoisomerase II)TUBB (Tubulin (alpha and beta subunits))mTOR (Mammalian target of rapamycin kinase)GR (Glucocorticoid receptor)
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