title: Final results of a multicenter phase 1 study of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia.
abstract: Based on clinical activity in phase 2 studies, lenalidomide was evaluated in a phase 2/3 study in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Following tumor lysis syndrome (TLS) complications, the protocol was amended to a phase 1 study to identify the maximum tolerated dose-escalation level (MTDEL). Fifty-two heavily pretreated patients, 69% with bulky disease and 48% with high-risk genomic abnormalities, initiated lenalidomide at 2.5 mg/day, with dose escalation until the MTDEL or the maximum assigned dose was attained. Lenalidomide was safely titrated to 20 mg/day; the MTDEL was not reached. Most common grade 3-4 adverse events were neutropenia and thrombocytopenia; TLS was mild and rare. The low starting dose and conservative dose escalation strategy resulted in six partial responders and 30 patients obtaining stable disease. In summary, lenalidomide 2.5 mg/day is a safe starting dose that can be titrated up to 20 mg/day in patients with CLL.
authors: Department I of Internal Medicine, Center of Integrated Oncology (CIO), CECAD, University of Cologne, Cologne, Germany. clemens.wendtner@uni-koeln.de
authors: Clemens-Martin
authors: CM
authors: Wendtner
authors: Peter
authors: P
authors: Hillmen
authors: Daruka
authors: D
authors: Mahadevan
authors: Andreas
authors: A
authors: Bühler
authors: Lutz
authors: L
authors: Uharek
authors: Steven
authors: S
authors: Coutré
authors: Olga
authors: O
authors: Frankfurt
authors: Adrian
authors: A
authors: Bloor
authors: Francesc
authors: F
authors: Bosch
authors: Richard R
authors: RR
authors: Furman
authors: Eva
authors: E
authors: Kimby
authors: John G
authors: JG
authors: Gribben
authors: Marco
authors: M
authors: Gobbi
authors: Luke
authors: L
authors: Dreisbach
authors: David D
authors: DD
authors: Hurd
authors: Mikkael A
authors: MA
authors: Sekeres
authors: Alessandra
authors: A
authors: Ferrajoli
authors: Sheetal
authors: S
authors: Shah
authors: Jennie
authors: J
authors: Zhang
authors: Laure
authors: L
authors: Moutouh-de Parseval
authors: Michael
authors: M
authors: Hallek
authors: Nyla A
authors: NA
authors: Heerema
authors: Stephan
authors: S
authors: Stilgenbauer
authors: Asher A
authors: AA
authors: Chanan-Khan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012008:Recurrence; D016879:Salvage Therapy; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced; D015275:Tumor Lysis Syndrome / Q000209:etiology / Q000517:prevention & control; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D013792:Thalidomide; D000493:Allopurinol; D000077269:Lenalidomide; D014740:Vidarabine; C024352:fludarabine