Complete Remissions of Adult T-cell Leukemia with Anti-CD25 Recombinant Immunotoxin LMB-2 and Chemotherapy to Block Immunogenicity

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Robert J KreitmanIra Pastan

Abstract

Adult T-cell leukemia (ATL) is usually CD25(+) and rapidly fatal. Anti-CD25 recombinant immunotoxin LMB-2 had phase I activity limited by immunogenicity and rapid growth. To prevent antidrug antibodies and leukemic progression between cycles, a phase II trial was performed with LMB-2 after cyclophosphamide and fludarabine. ATL patients received cyclophosphamide and fludarabine days 1 to 3 and 2 weeks later began up to 6 cycles at 3-week intervals of cyclophosphamide and fludarabine days 1 to 3 followed by LMB-2 30-40 μg/kg i.v. days 3, 5, and 7. Three different dose levels of cyclophosphamide and fludarabine were used, 20+200 (n = 3), 25+250 (n = 12), and 30+300 mg/m(2) (n = 2). Of 17 patients enrolled and treated with fludarabine and cyclophosphamide for cycle-1, 15 received subsequent cycle(s) containing LMB-2 and were therefore evaluable for response. Lack of antibody formation permitted retreatment in most patients. Of 10 evaluable leukemic patients receiving 25+250 or 30+300 mg/m(2) of fludarabine and cyclophosphamide, 6 (60%) achieved complete remission (CR) and 2 (20%) partial remission (PR), and all 5 with >25% leukemic cells achieved CR. No responses were achieved in 5 with lymphomatous ATL or lower fludarabine and cyc...Continue Reading

Associated Clinical Trials

Jun 18, 2009·Robert Kreitman, M.D., Robert Kreitman, M.D.

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Citations

Jul 28, 2006·Journal of Pharmacological and Toxicological Methods·Behzad ForoutanDiana Anderson
Jun 3, 2016·Scientific Reports·Ting LiYong Juan Zhao
Mar 11, 2017·International Reviews of Immunology·Bahman AkbariLeila Rahbarnia
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Jun 4, 2019·International Reviews of Immunology·Amit Sharma, Dipayan Rudra
Oct 28, 2019·Oncoimmunology·Raquel Ibáñez-PérezAlberto Anel
May 31, 2017·British Journal of Haematology·Michael J Flynn, John A Hartley
Aug 7, 2020·Biomolecules·Robert J Kreitman, Ira Pastan
Nov 2, 2019·Journal of Pharmaceutical Sciences·Ji-Sun KimYong-Sung Kim
Jan 30, 2021·Life Sciences·Vahid KarpishehFarhad Jadidi-Niaragh
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Apr 29, 2021·Seminars in Hematology·Kenji Ishitsuka
May 28, 2019·International Journal of Biological Macromolecules·Zeinab Amiri TehranizadehMohammad Reza Saberi

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