A Phase II Study of CLAG Regimen Combined With Imatinib Mesylate for Relapsed or Refractory Acute Myeloid Leukemia

Given the lack of standard salvage chemotherapy regimen for relapsed or refractory (RR) acute myeloid leukemia (AML), a phase 2 clinical study of cladribine, cytarabine, G-CSF (CLAG) regimen in combination with imatinib mesylate (IM) in patients with RR-AML was conducted at the Moffitt Cancer Center. Between August 2009 and April 2011,38 patients were treated and the overall response rate was 37% with a median overall survival of 11.1 month. Among responders, 8/14 patients proceeded to allogeneic hematopoietic cell transplant. Overall, CLAG plus IM was well tolerated, with encouraging signs of activity in patients with poor-risk AML. Introduction: No standard salvage chemotherapy regimen is available for relapsed or refractory (RR) acute myeloid leukemia (AML). Preclinical data have suggested synergy in vitro between cytarabine and imatinib mesylate (IM) on AML cell growth inhibition. After demonstrating the safety and feasibility in a phase I study, we conducted a phase II clinical study of CLAG (cladribine, cytarabine, granulocyte colony-stimulating factor) regimen combined with IM for patients with RR-AML. Patients and Methods: We performed a single-institution 2-stage phase II study. The primary endpoint was the remission rate measured using the standard AML response criteria. The secondary endpoints included overall survival (OS) and progression-free survival (PFS). Results: From August 2009 to April 2011, 38 patients were treated at the Moffitt Cancer Center. Their median age was 62 years (range, 26-79 years). Of the 38 patients, 7 (18%) had refractory AML, 19 (50%) had early relapse, and 12 (32%) had late relapse. At the original diagnosis, only 2 patients had favorable risk factors, 18 had intermediate risk, and 16 had poor risk; for 2 patients, the karyotype was missing. The overall response rate for all 38 evaluable patients was 37%. The median OS was 11.1 months (95% Cl, 4.8-13.4 months), the median PFS was 4.9 months (95% Cl, 1.6-11.7 months). Among the responders, 8 of 14 patients subsequently underwent allogeneic hematopoietic cell transplantation. Conclusion: CLAG plus IM was well tolerated, with encouraging signs of activity in patients with poor-risk AML.