| Abstract: |
BACKGROUND: Patients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemotherapy. Effective therapies with acceptable side-effect profiles are needed for this patient population. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and safety of idelalisib, an oral inhibitor of the delta isoform of phosphatidylinositol 3-kinase, in combination with rituximab versus rituximab plus placebo. We randomly assigned 220 patients with decreased renal function, previous therapy-induced myelosuppression, or major coexisting illnesses to receive rituximab and either idelalisib (at a dose of 150 mg) or placebo twice daily. The primary end point was progression-free survival. At the first prespecified interim analysis, the study was stopped early on the recommendation of the data and safety monitoring board owing to overwhelming efficacy. RESULTS: The median progression-free survival was 5.5 months in the placebo group and was not reached in the idelalisib group (hazard ratio for progression or death in the idelalisib group, 0.15; P<0.001). Patients receiving idelalisib versus those receiving placebo had improved rates of overall response (81% vs. 13%; odds ratio, 29.92; P<0.001) and overall survival at 12 months (92% vs. 80%; hazard ratio for death, 0.28; P=0.02). Serious adverse events occurred in 40% of the patients receiving idelalisib and rituximab and in 35% of those receiving placebo and rituximab. CONCLUSIONS: The combination of idelalisib and rituximab, as compared with placebo and rituximab, significantly improved progression-free survival, response rate, and overall survival among patients with relapsed CLL who were less able to undergo chemotherapy. Copyright © 2014 Massachusetts Medical Society. |
| Keywords: |
adult; cancer survival; controlled study; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; major clinical study; overall survival; constipation; fatigue; neutropenia; placebo; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; drug withdrawal; monotherapy; rituximab; lymph nodes; progression free survival; anemia; nausea; randomized controlled trial; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; recurrence; pneumocystis pneumonia; cancer mortality; chill; coughing; dyspnea; febrile neutropenia; fever; pneumonia; rash; kidney function; multicenter study; drug response; sepsis; purines; skin disease; phase 3 clinical trial; leukemia relapse; double blind procedure; double-blind method; chronic lymphatic leukemia; gastrointestinal disease; leukemia, lymphocytic, chronic, b-cell; night sweat; cellulitis; decreased appetite; kaplan-meier estimate; hypertransaminasemia; kidney diseases; antibodies, monoclonal, murine-derived; idelalisib; infusion related reaction; very elderly; humans; human; male; female; priority journal; article; class ia phosphatidylinositol 3-kinase; quinazolinones
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