title: Reduced occurrence of tumor flare with flavopiridol followed by combined flavopiridol and lenalidomide in patients with relapsed chronic lymphocytic leukemia (CLL).
abstract: Flavopiridol and lenalidomide have activity in refractory CLL without immunosuppression or opportunistic infections seen with other therapies. We hypothesized that flavopiridol treatment could adequately de-bulk disease prior to lenalidomide therapy, decreasing the incidence of tumor flare with higher doses of lenalidomide. In this Phase I study, the maximum tolerated dose was not reached with treatment consisting of flavopiridol 30 mg m(-2) intravenous bolus (IVB) + 30 mg m(-2) continuous intravenous infusion (CIVI) cycle (C) 1 day (D) 1 and 30 mg m(-2) IVB + 50 mg m(-2) CIVI C1 D8,15 and C2-8 D3,10,17 with lenalidomide 15 mg orally daily C2-8 D1-21. There was no unexpected toxicity seen, including no increased tumor lysis, tumor flare (even at higher doses of lenalidomide) or opportunistic infection. Significant clinical activity was demonstrated, with a 51% response rate in this group of heavily pretreated patients. Biomarker testing confirmed association of mitochondrial priming of the BH3 only peptide Puma with response.
authors: Division of Hematology, Department of Internal Medicine, The Ohio State University, Comprehensive Cancer Center, The Ohio State University, College of Pharmacy, The Ohio State University, Ohio.
authors: Kami
authors: K
authors: Maddocks
authors: Lai
authors: L
authors: Wei
authors: Darlene
authors: D
authors: Rozewski
authors: Yao
authors: Y
authors: Jiang
authors: Yuan
authors: Y
authors: Zhao
authors: Mikhil
authors: M
authors: Adusumilli
authors: William E
authors: WE
authors: Pierceall
authors: Camille
authors: C
authors: Doykin
authors: Michael H
authors: MH
authors: Cardone
authors: Jeffrey A
authors: JA
authors: Jones
authors: Joseph
authors: J
authors: Flynn
authors: Leslie A
authors: LA
authors: Andritsos
authors: Michael R
authors: MR
authors: Grever
authors: John C
authors: JC
authors: Byrd
authors: Amy J
authors: AJ
authors: Johnson
authors: Mitch A
authors: MA
authors: Phelps
authors: Kristie A
authors: KA
authors: Blum
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D015275:Tumor Lysis Syndrome / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; D013792:Thalidomide; D000077269:Lenalidomide
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