A Phase II study of Bcl-2 antisense (oblimersen sodium) combined with gemtuzumab ozogamicin in older patients with acute myeloid leukemia in first relapse

Joseph Moore; Karen Seiter; Jonathan Kolitz; Wendy Stock; Francis Giles; Matt Kalaycio; David Zenk; Guido Marcucci

doi:10.1016/j.leukres.2005.10.025

A Phase II study of Bcl-2 antisense (oblimersen sodium) combined with gemtuzumab ozogamicin in older patients with acute myeloid leukemia in first relapse

Leuk Res. 2006 Jul;30(7):777-83. doi: 10.1016/j.leukres.2005.10.025. Epub 2006 May 26.

Authors

Joseph Moore¹, Karen Seiter, Jonathan Kolitz, Wendy Stock, Francis Giles, Matt Kalaycio, David Zenk, Guido Marcucci

Affiliation

¹ Duke University Medical Center, Morris Cancer Clinics, P.O. Box 3872, Durham, NC 27710, United States. manusub@aol.com

PMID: 16730060
DOI: 10.1016/j.leukres.2005.10.025

Abstract

Oblimersen selectively targets Bcl-2 mRNA and has been shown to enhance the apoptotic activity of various antileukemic agents, including gemtuzumab ozogamicin (GO), in preclinical studies. We evaluated the efficacy and safety of oblimersen combined with GO in patients > or =60 years of age in first relapse with CD33+ acute myeloid leukemia. Oblimersen 7 mg/kg/day was given as a continuous intravenous infusion on days 1-7 and 15-21. GO 9 mg/m2 was given intravenously on days 4 and 18. Twelve of 48 patients (25%) achieved a major response (five, complete response and seven, complete response without platelet recovery). Ten of the 12 patients who achieved a major response survived >6 months compared with six of 36 non-responders. Serious adverse events for the oblimersen/GO combination were qualitatively similar to those reported for GO alone. Oblimersen can be safely combined with GO. Assessment of incremental benefit will require a randomized trial.

Publication types

Clinical Trial, Phase II
Multicenter Study

MeSH terms

Acute Disease
Aged
Aminoglycosides / administration & dosage*
Aminoglycosides / adverse effects
Antibodies, Monoclonal / administration & dosage*
Antibodies, Monoclonal / adverse effects
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Cytogenetic Analysis
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug-Related Side Effects and Adverse Reactions
Female
Follow-Up Studies
Gemtuzumab
Humans
Infusions, Intravenous
Leukemia, Myeloid / diagnosis
Leukemia, Myeloid / drug therapy*
Leukemia, Myeloid / genetics
Male
Maximum Tolerated Dose
Recurrence
Risk Factors
Survival Rate
Thionucleotides / administration & dosage*
Thionucleotides / adverse effects
Thionucleotides / therapeutic use*
Treatment Outcome

Substances

Aminoglycosides
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Thionucleotides
oblimersen
Gemtuzumab