Related Experiment Video
Updated: Sep 11, 2026
Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation
Published on: November 10, 2017
ENCERT: A Multisite Phase 1 Trial Using Everolimus in Combination With Nelarabine, Cyclophosphamide, and Etoposide in
Himalee S Sabnis1,2, Melinda Pauly1,2, Eric S Schafer3
1Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
Background:
Relapsed and refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LL) remains a therapeutic challenge. Allogeneic hematopoietic stem cell transplantation (HSCT) after achieving complete remission (CR) offers the only chance of cure, but effective modalities to achieve CR are limited. Activation of mTOR and PI3K pathways has been well described in T-ALL and monotherapy with mTOR inhibitors has shown efficacy signals used in relapsed disease.
Methods:
This multisite Phase 1 study evaluated the safety, tolerability, and anti-leukemic activity of everolimus with NEC chemotherapy (nelarabine, etoposide, and cyclophosphamide) among children and young adults with relapsed/refractory T-ALL/T-LL.
Results:
Eight patients were enrolled to two dose levels (DLs) on this study and no dose-limiting toxicities were reported. Most adverse events related to therapy were expected and hematological. DL2 (n = 5) of everolimus at 5 mg/m2/day was the highest dose tested. The overall response rate (complete response + complete response with incomplete platelet recovery + partial response) was 75% (6/8) with 100% (5/5) responses in the T-ALL cohort and 33% (1/3) responses in T-LL cohort. All six patients who obtained a PR or greater proceeded to receive HSCT as consolidation therapy. Two of the six patients transplanted are alive today with two deaths related to progressive disease and two related to veno-occlusive disease post transplantation.
Conclusions:
This study demonstrates safety with a combination of everolimus and NEC chemotherapy. Given the observed tolerability and efficacy of everolimus with NEC in this small cohort of patients, this combination should be further evaluated in larger phase 2/3 clinical trials.
Trial Registration:
ClinicalTrials.gov identifier: NCT03328104.
