A Phase 2 Study of Ruxolitinib with Chemotherapy in Children with Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (INCB18424-269/AALL1521): Dose-Finding Results from the Part 1 Safety Phase

We report the initial safety of ruxolitinib in combination with post-induction chemotherapy in children and AYAs with newly-diagnosed high-risk (HR) Ph-like ALL with CRLF2-R or other JAK pathway alterations treated on the non-randomized, 2-part phase 2 study INCB18424-269 (AALL1521; NCT02723994).Methods: Patients aged 1-21 years at time of diagnosis with HR B-ALL and eligible Ph-like genetic lesions who had completed 4-drug induction chemotherapy as per the Children's Oncology Group (COG) AALL1131 study (NCT02883049) were eligible to participate. Patients were stratified into 4 cohorts by genetic alterations and end-induction flow cytometric minimal residual disease (MRD) status: cohort A = CRLF2-R JAK-mutant, MRD+; B = CRLF2-R JAK-wild-type, MRD+; C = other JAK pathway alterations, MRD+, D = any CRLF2-R or JAK pathway alteration, MRD-. Patients commenced treatment on the INCB18424-269/AALL1521 study at consolidation with ruxolitinib orally twice daily in combination with augmented Berlin-Frankfurt-Münster (aBFM) post-induction chemotherapy as per AALL1131. Five discontinuous dose levels (10-50 mg/m2/dose 14-days-on/14-days-off per cycle [DL-2 to DL2]) and one continuous DL1b (40 mg/m2/dose x 28 days per cycle) of ruxolitinib with aBFM chemotherapy were explored via a standard rolling 6 design. Dose-limiting toxicities (DLTs) were assessed through Day 29 of delayed intensification (DI) and defined as hematologic and non-hematologic toxicity with higher grade or more prol...
Source: Blood - Category: Hematology Authors: Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Targeted Therapy in ALL: Immunotherapy and Beyond Source Type: research