Addition of AEG35156 XIAP antisense oligonucleotide in reinduction chemotherapy does not improve remission rates in patients with primary refractory acute myeloid leukemia in a randomized phase II study.

Abstract

BACKGROUND:

XIAP (X-linked inhibitor of apoptosis protein) is an inhibitor of caspases 3 and 9 that is overexpressed in acute myeloid leukemia (AML) and may contribute to chemoresistance. We report an open-label randomized phase II trial of reinduction chemotherapy with and without the XIAP antisense oligonucleotide AEG35156 in patients with AML who did not achieve remission with initial induction chemotherapy.

METHODS:

Twenty-seven patients with AML who were refractory to initial induction chemotherapy were randomized and treated with AEG35156 (650 mg) in combination with high-dose cytarabine and idarubicin. Thirteen patients were randomized and treated with high-dose cytarabine and idarubicin alone. The rates of response and toxicity were determined.

RESULTS:

Of the 27 patients assigned to AEG35156 in combination with high-dose cytarabine and idarubicin, 3 died during reinduction chemotherapy, 5 achieved complete remission (CR), and 6 achieved CR with incomplete platelet count recovery (CRp), for an overall response rate of 41%. Of the 13 patients assigned to the control arm of the study, none died during reinduction, 6 achieved CR, and 3 achieved CRp, for an overall response rate of 69%. The differences in response rates between patients in the AEG35156 and control arms were not statistically different (P = 0.18 by the χ(2) test).

CONCLUSIONS:

The addition of AEG35156 to reinduction chemotherapy was well tolerated but did not improve rates of remission. Therefore alternative therapeutic strategies should be explored in patients with AML refractory to induction chemotherapy.

• Authors: Aaron D Schimmer, Wolfgang Herr, Mathias Hänel, Gautham Borthakur, Arthur Frankel, Heinz-August Horst, Sonja Martin, Jeannine Kassis, Pierre Desjardins, Karen Seiter, Walter Fiedler, Richard Noppeney, Aristoteles Giagounidis, Christine Jacob, Jacques Jolivet, Martin S Tallman, Steffen Koschmieder
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 11 Issue 5 Pg. 433-8 (Oct 2011) ISSN: 2152-2669 [Electronic] United States
• PMID: 21729686 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• AEG 35156
• Oligonucleotides
• X-Linked Inhibitor of Apoptosis Protein
• XIAP protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Female
• Humans
• Leukemia, Myeloid, Acute (drug therapy, genetics)
• Male
• Middle Aged
• Oligonucleotides (administration & dosage)
• Remission Induction
• Treatment Outcome
• X-Linked Inhibitor of Apoptosis Protein (antagonists & inhibitors, genetics)
• Young Adult