Failure of three novel regimens to improve outcome for patients with relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative Oncology Group.
The treatment of relapsed acute myeloid leukaemia (AML) remains unsatisfactory. We conducted a phase II randomized trial where patients received intermediate-dose cytarabine for 4 d followed by gemtuzumab ozogamicin on day 5 (Arm A), or combined with liposomal daunorubicin for 3 d (Arm B), or cytarabine given for 5 d combined with cyclophosphamide for 3 d and topotecan by continuous infusion for 5 d (Arm C). Eligible patients had primary refractory AML, a first relapse after a remission of <1 year, or a second or greater relapse. The primary objective of this trial was attainment of a conventional complete remission (CR) or a CR without platelet recovery (CRp) in at least 40% of patients. The CR/CRp rates for the 82 eligible patients were 3/26 (12%) in Arm A, 2/29 (7%) in Arm B, and 1/27 (4%) in Arm C. No patients who had relapsed within 6 months of initial CR or who had suffered multiple relapses responded. More than 95% of patients subsequently died of AML. No unexpected toxicities were encountered. We conclude that none of these three regimens were effective enough in the treatment of high-risk relapsed or refractory AML to warrant further study. This trial was registered at http://www.clinicaltrials.gov as #NCT00005962.
Mayo Clinic, Rochester, MN 55905, USA. litzow.mark@mayo.edu
Mark R
MR
Litzow
Megan
M
Othus
Larry D
LD
Cripe
Steven D
SD
Gore
Hillard M
HM
Lazarus
Sandra J
SJ
Lee
John M
JM
Bennett
Elisabeth M
EM
Paietta
Gordon W
GW
Dewald
Jacob M
JM
Rowe
Martin S
MS
Tallman
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D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D008081:Liposomes; D003561:Cytarabine; D019772:Topotecan; D003520:Cyclophosphamide; D000079982:Gemtuzumab; D003630:Daunorubicin