BACKGROUND: Outcomes for children with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) are dismal. In an effort to improve outcomes, we performed a phase I/II study of a novel clofarabine based combination regimen called TVTC. Herein, we report the response rates of patients in the phase II portion of the study. PROCEDURE: Seventeen patients with R/R ALL, AML, or biphenotypic leukemia were enrolled. Sixteen patients were evaluable for response. Patients were treated at the maximum tolerated dose (MTD) from the phase I portion of the study (clofarabine 40 mg/m(2) /day IV × 5 days, topotecan 1 mg/m(2) /day IV continuous infusion × 5 days, vinorelbine 20 mg/m(2) /week IV × 3 weeks, thiotepa 15 mg/m(2)/day IV × 1 day). The primary endpoint was overall response rate (ORR), defined as CR or CR without platelet recovery (CRp). RESULTS: The ORR was 69% (10 CR, 1 CRp). Among the 11 responders, 9 (82%) proceeded to hematopoietic stem cell transplantation. The most common grade 3+ non-hematologic toxicities were febrile neutropenia (82%) and transient transaminase elevation (47%). CONCLUSIONS: TVTC demonstrates significant activity in patients with R/R acute leukemia. The activity in R/R AML patients was very encouraging, with 8 of 12 (67%) patients achieving a CR/CRp. Patients with high risk de novo AML may benefit from incorporation of TVTC therapy into frontline treatment regimens. This regimen warrants further exploration in a larger cohort of patients with R/R leukemia.
BACKGROUND: Outcomes for children with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) are dismal. In an effort to improve outcomes, we performed a phase I/II study of a novel clofarabine based combination regimen called TVTC. Herein, we report the response rates of patients in the phase II portion of the study. PROCEDURE: Seventeen patients with R/R ALL, AML, or biphenotypic leukemia were enrolled. Sixteen patients were evaluable for response. Patients were treated at the maximum tolerated dose (MTD) from the phase I portion of the study (clofarabine 40 mg/m(2) /day IV × 5 days, topotecan 1 mg/m(2) /day IV continuous infusion × 5 days, vinorelbine 20 mg/m(2) /week IV × 3 weeks, thiotepa 15 mg/m(2)/day IV × 1 day). The primary endpoint was overall response rate (ORR), defined as CR or CR without platelet recovery (CRp). RESULTS: The ORR was 69% (10 CR, 1 CRp). Among the 11 responders, 9 (82%) proceeded to hematopoietic stem cell transplantation. The most common grade 3+ non-hematologic toxicities were febrile neutropenia (82%) and transient transaminase elevation (47%). CONCLUSIONS:TVTC demonstrates significant activity in patients with R/R acute leukemia. The activity in R/R AMLpatients was very encouraging, with 8 of 12 (67%) patients achieving a CR/CRp. Patients with high risk de novo AML may benefit from incorporation of TVTC therapy into frontline treatment regimens. This regimen warrants further exploration in a larger cohort of patients with R/R leukemia.
Authors: Kari L Bjornard; Laura S Gilchrist; Hiroto Inaba; Barthelemy Diouf; Marilyn J Hockenberry; Nina S Kadan-Lottick; Daniel C Bowers; M Eileen Dolan; Nicole J Ullrich; William E Evans; Kirsten K Ness Journal: Lancet Child Adolesc Health Date: 2018-09-01
Authors: Sanam Shahid; Kavitha Ramaswamy; Jessica Flynn; Audrey Mauguen; Karlo Perica; Jae H Park; Christopher J Forlenza; Neerav N Shukla; Peter G Steinherz; Steven P Margossian; Jaap Jan Boelens; Nancy A Kernan; Kevin J Curran Journal: Transplant Cell Ther Date: 2021-11-28
Authors: Barbara Spitzer; Miguel-Angel Perales; Nancy A Kernan; Susan E Prockop; Emily C Zabor; Nicholas Webb; Hugo Castro-Malaspina; Esperanza B Papadopoulos; James W Young; Andromachi Scaradavou; Rachel Kobos; Sergio A Giralt; Richard J O'Reilly; Farid Boulad Journal: Biol Blood Marrow Transplant Date: 2016-05-13 Impact factor: 5.742
Authors: C Michel Zwaan; Edward A Kolb; Dirk Reinhardt; Jonas Abrahamsson; Souichi Adachi; Richard Aplenc; Eveline S J M De Bont; Barbara De Moerloose; Michael Dworzak; Brenda E S Gibson; Henrik Hasle; Guy Leverger; Franco Locatelli; Christine Ragu; Raul C Ribeiro; Carmelo Rizzari; Jeffrey E Rubnitz; Owen P Smith; Lillian Sung; Daisuke Tomizawa; Marry M van den Heuvel-Eibrink; Ursula Creutzig; Gertjan J L Kaspers Journal: J Clin Oncol Date: 2015-08-24 Impact factor: 44.544