Ruxolitinib + hyper-CVAD chemotherapy in R/R Ph-like ALL: Phase I/II data

Results from a phase I/II trial (NCT02420717) investigating the safety and efficacy of ruxolitinib in combination with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) chemotherapy in 11 patients with relapsed/refractory (R/R) Philadelphia chromosome-like (Ph-like) B-cell acute lymphoblastic leukemia (B-ALL) were published by Goulart et al. in Clinical Lymphoma, Myeloma & Leukemia. The primary endpoint for the phase I portion was safety with dose-limiting toxicities (DLTs) assessed at 15 mg twice daily (BID) (dose level 1 [DL1]), 20 mg BID (DL2), and 25 mg BID (DL3) of ruxolitinib (Cohort 1; n = 10), while the primary endpoint of the phase II portion was composite response rate (CRc), defined as patients achieving either complete response (CR) or CR with incomplete blood count recovery (CRi). 

Key data: No dose-limiting toxicities (DLT) were observed at DL1 and DL2. Enrollment to DL3 was terminated early due to slow accrual. The most common Grade ≥3 adverse events (AEs) were sepsis (n = 8), febrile neutropenia (n = 7), pneumonia (n = 4), pain (n = 3), elevated bilirubin (n = 3), and hypotension (n = 3). One out of ten patients receiving ruxolitinib DL2 achieved a measurable residual disease (MRD)-positive CR with incomplete platelet recovery (CRp). The median overall survival (OS) was 4.9 months. 

Key learning: The findings demonstrate that while the combination of ruxolitinib and hyper-CVAD was safe and tolerable in patients with R/R Ph-like ALL, clinical efficacy was limited, supporting the need to explore alternative treatment strategies in this high-risk patient population.