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Leuk Res. 2013 Oct;37(10):1195-9. doi: 10.1016/j.leukres.2013.06.006. Epub 2013 Jul 15.

Cyclophosphamide, alvocidib (flavopiridol), and rituximab, a novel feasible chemoimmunotherapy regimen for patients with high-risk chronic lymphocytic leukemia.

Author information

1
Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, United States. deborah.stephens@osumc.edu

Abstract

Alvocidib has demonstrated efficacy in high-risk chronic lymphocytic leukemia (CLL) patients. In this phase I study, we combined cyclophosphamide, alvocidib and rituximab (CAR) in a schema designed to mitigate tumor lysis syndrome (TLS) seen previously with alvocidib. Nine nucleoside analog-naïve, high-risk patients received escalating doses of CAR therapy. Dose limiting toxicity was not experienced. No instances of TLS were observed. Patient responses included three complete remissions and four partial remissions. CAR was tolerable and active in high-risk CLL patients without TLS toxicity. With continued monitoring of toxicities, a phase Ib/II study of this combination as frontline therapy is warranted.

KEYWORDS:

Alvocidib; B2M; CAR; CDK; CLL; CR; CRS; Chemoimmunotherapy; Chronic lymphocytic leukemia; Cyclin-dependent kinase inhibitor; DLT; Del(11q); Del(17p); ECOG; Eastern Cooperative Oncology Group; FC(R); Flavopiridol; High-risk cytogenetics; IgV(H); MTD; NCI; National Cancer Institute; ORR; OS; PD; PFS; PK; TLS; WBC; beta 2 microglobulin; chronic lymphocytic leukemia; complete response; cyclin-dependent kinase; cyclophophamide, alvocidib, rituximab; cytokine release syndrome; dose limiting toxicity; fludarabine, cyclophosphamide, (rituximab); immunoglobulin heavy chain variable region; maximum tolerated dose; overall response rate; overall survival; pharmacokinetic; progression-free survival; progressive disease; tumor lysis syndrome; white blood cell

PMID:
23867058
PMCID:
PMC3934299
DOI:
10.1016/j.leukres.2013.06.006
[Indexed for MEDLINE]
Free PMC Article
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