Phase 2 Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory (R/R) Acute Lymphoblastic Leukemia (ALL)

In children with relapsed ALL, salvage options are sub-optimal and relapse remains the leading cause of death. Achieving subsequent complete remission (CR) after relapse is a critical first step to cure, without which, survival is unlikely. A phase 1b trial evaluating carfilzomib combined with VXLD (vincristine, dexamethasone, PEG-asparaginase, daunorubicin) in children with relapsed ALL showed preliminary safety and efficacy in highly advanced pediatric ALL (Burke, ASH 2019). The phase 1b portion of this trial was recently completed and a recommended phase 2 dose determined. Patients (pts) were heterogeneous with respect to number of relapses (>1, n = 7), refractory relapse (n = 7), prior stem cell transplant (n = 8) and duration of first remission (<18 mo, n = 15), or none of these risk factors (n = 3). CR with incomplete hematologic recovery or better occurred in 50% overall after 1 cycle of induction (9 of 13 [69%] with B-ALL; 3 of 11 [27%] with T-ALL) and increased to 58% after consolidation (B-ALL, 9 of 13 [69%]; T-ALL, 5 of 11 [45%]). Herein, we describe the design of the phase 2 study (NCT02303821) which is currently enrolling.