A Phase I Study of Venetoclax in Combination with Cytotoxic Chemotherapy, Including Calaspargase Pegol, for Children, Adolescents and Young Adults with High-Risk Hematologic Malignancies

Pediatric Blood Cancer
Andrew Place, MD, PhD
Dana-Farber Cancer Institute


Effective treatment for children and young adults with relapsed/refractory MDS, MDS-associated AML (MDS/AML), treatment related MDS/AML, and relapsed/refractory high-risk ALL/LBL continues to be a major clinical challenge with poor long-term survival and significant unmet need. Conventional chemotherapy exerts cytotoxic (toxic to cells) effects and induces a cascade of events that ultimately lead to a process called apoptosis (or programmed cell death). One mechanism by which hematologic (blood) malignancies are thought to arise is through a dysregulated apoptotic pathway in which cancer cells evade programmed cell death. Overexpression of BCL2 prevents cancer cells from being killed by inhibiting apoptosis despite cytotoxic therapy or immune cell attacks on cancer cells. Venetoclax is a drug that targets and inhibits the BCL2 family of proteins. Novel targeted therapies, such as venetoclax, that may reverse chemotherapy resistance and synergize with standard of care chemotherapy are ideal agents for treatment in these high-risk populations. This phase I study will determine the safety and tolerability of venetoclax in combination with chemotherapy in the myeloid and lymphoid hematologic malignancies listed above.

Trial Registration: ClinicalTrials.gov Identifier: NCT05292664