Phase 1b study of carfilzomib with induction chemotherapy in pediatric relapsed/refractory acute lymphoblastic leukemia

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in childhood. Survival for patients following relapse remains poor, and achieving complete remission (CR) after relapse is the first critical step to cure. Carfilzomib is a proteasome inhibitor with an acceptable safety profile and clinical activity in adults with multiple myeloma but has not been assessed in children. The primary objective of this phase 1b study was to assess the safety and tolerability of carfilzomib combined with vincristine, dexamethasone, asparaginase, and daunorubicin (VXLD) in children with relapsed and/or refractory ALL.Methods: Patients aged 1-21 years (n = 24) received 4-week induction therapy with carfilzomib at dose levels of 27 mg/m 2 (n = 3), 36 mg/m 2 (n = 7), 45 mg/m 2 (n = 4), and 56 mg/m 2 (n = 10) in combination with VXLD. Patients achieving stable disease

Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment

“…With the in-depth research on tumor therapeutic targets, chemotherapeutic drugs with different targets and pathways of action have started to adopt a combination therapy strategy to deal with the malignant development of tumors [ 8 , 9 ]. However, considering the more serious adverse effects of chemotherapeutic drugs, the combination of chemotherapeutic drugs with less toxic natural compounds that contribute to tumor management is gradually becoming one of the new strategies for tumor treatment.…”

Translational advances in the treatment of childhood acute lymphoblastic leukemia: narrative review of current and emerging molecular and immunotherapies

“…Other proteasome inhibitors are in the pipeline, including carfilzomib, for which a phase 1b trial in r/r ALL has been completed (75), and ixazomib. More data will be needed for us to better understand the role of proteasome inhibitors in the treatment of acute leukemia.…”