title: Cyclophosphamide, alvocidib (flavopiridol), and rituximab, a novel feasible chemoimmunotherapy regimen for patients with high-risk chronic lymphocytic leukemia.
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.
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, United States. deborah.stephens@osumc.edu
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Stephens
authors.forename: Amy S
authors.initials: AS
authors.lastname: Ruppert
authors.forename: Kami
authors.initials: K
authors.lastname: Maddocks
authors.forename: Leslie
authors.initials: L
authors.lastname: Andritsos
authors.forename: Robert
authors.initials: R
authors.lastname: Baiocchi
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jones
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Johnson
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Smith
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Ling
authors.forename: Junan
authors.initials: J
authors.lastname: Li
authors.forename: Mitch A
authors.initials: MA
authors.lastname: Phelps
authors.forename: Michael R
authors.initials: MR
authors.lastname: Grever
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Flynn
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010880:Piperidines / Q000008:administration & dosage; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; D000069283:Rituximab; D003520:Cyclophosphamide
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