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.
Litzow
Mark R
MR
Mayo Clinic, Rochester, MN 55905, USA. litzow.mark@mayo.edu
Othus
Megan
M
Cripe
Larry D
LD
Gore
Steven D
SD
Lazarus
Hillard M
HM
Lee
Sandra J
SJ
Bennett
John M
JM
Paietta
Elisabeth M
EM
Dewald
Gordon W
GW
Rowe
Jacob M
JM
Tallman
Martin S
MS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D019772:Topotecan / Q000627:therapeutic use
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