SAN DIEGO, CA—Rami S. Komrokji, MD, from H. Lee Moffitt Cancer Center & Research Institute in Tampa, FL, and colleagues reported study data indicating that the CLAG regimen (cladribine, cytarabine, granulocyte colony stimulating factor) in combination with imatinib mesylate showed encouraging signs of activity in relapsed or refractory (RR) acute myeloid leukemia (AML). Results of this single-institution, two-stage, Phase 2 study were presented at the 53rd American Society of Hematology Annual Meeting and Exposition.

Relapse was defined as evidence of disease following documented CR (complete response) or incomplete count recovery (CRi) to the most recent prior regimen (either early [≤12 months] or late [>12 months]). Patients included in the study had either RR-AML or chronic myeloid leukemia (CML) blast crisis. Key exclusion criteria were: ECOG performance status >2, inadequate kidney or liver function tests, history of chronic liver disease, hepatitis, or HIV infection, prior therapy with CLAG regimen, or active systemic infection. From August 2009 to April 2011, 38 patients were treated and evaluable. Seven patients (18%) had refractory AML, 19 (50%) had early relapse, and 12 (32%) had late relapse. Eight patients (21%) had prior MDS. Median age was 62 years (range 26–79); 58% were male and 87% were Caucasian.

The CLAG regimen consisted of cladribine 5mg/m2 as a 2-hour IV infusion Days 2–6, cytarabine 2g/m2 as a 4-hour IV infusion daily (starting 2 hours after cladribine) Days 2–6, granulocyte colony stimulating factor (G-CSF) 300mcg subcutaneously for 6 days starting 12–24 hours (Day 1) before the first dose of cladribine, and imatinib 400mg orally twice daily on Days 2–15.

The primary endpoint was remission rate measured by standard AML response criteria. Secondary endpoints included overall survival (OS) and progression free survival (PFS). After a median follow-up duration of 9.4 months, the overall response rate (CR + CRi) was 37% (26% CR, 11% CRi). CR/CRi occurred in 8 out of 26 early RR-AML patients (30.8%; 95%CI 14.3–51.8%) and 6 out of 12 late relapse patients (50%; 95% CI 21.1–78.9%). PR was observed in 13% and disease progression in 37%. Median OS was 11.1 months (95% CI 4.8–13.4), while the median PFS was 4.9 months (95% CI 1.6–11.7).

The CLAG regimen was generally well tolerated. The most common non-hematologic toxicities occurring in ≥50% of patients included edema (82%), nausea (71%), diarrhea (66%), febrile neutropenia (58%), and vomiting (50%). Febrile neutropenia was the most common ≥Grade 3 adverse event, which was reported in 58% of patients, followed by pneumonia (34%), sepsis (29%), hypokalemia (24%), gastrointestinal infection (16%), and diarrhea (11%). Two early deaths (within 30 days) occurred due to hemorrhage and hepatic failure.