AEG35156 has shown early evidence of activity in patients with advanced indolent B-cell lymphomas in Phase 1 trials and merits further evaluation in this disease. This trial is designed to determine the recommended dose of AEG35156 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and indolent B-cell lymphomas.
Apoptotic induction in cancer cells is a sought after therapeutic goal. Most successful anticancer agents activate apoptosis pathways in the cancers they treat. Apoptotic pathways in cells appear to converge on a single family of enzymes, the caspases, which are proteases that dismantle the cell in an orderly, non-inflammatory fashion, resulting in cell death. The X-linked Inhibitor of Apoptosis (XIAP) is the only known cellular inhibitor of caspases, its over expression thereby blocking the principal means of apoptosis. A wide range of evidence indicates that cellular overexpression of members of the IAP family is a fundamental means by which many cancer cells evade death, even in the presence of strong extrinsic (death receptor-mediated) and intrinsic (mitochondria-mediated) apoptotic cues. The inhibition of cellular XIAP activity, specifically in cancer cells under stress and primed for apoptosis by chemotherapeutic agents, is viewed as a powerful means of tipping the balance towards cell death. In particular, XIAP has been shown to be overexpressed in lymphoma. AEG35156 is a second generation antisense which targets XIAP mRNA to lower XIAP levels and the apoptotic threshold of cancer cells, enhancing their sensitivity to intrinsic death and chemotherapy. AEG35156 has shown early evidence of activity in patients with advanced indolent B-cell lymphomas in Phase 1 trials and merits further evaluation in this disease.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
AEG35156 will be given as a 2-hour intravenous infusion (escalating dose 50, 100, 150, 200, 250 and 300 mg) once weekly on Day 1, Day 8 and Day 15. One cycle of therapy will consist of 21 days. Patients will be treated until disease progression. * Patients must be pretreated for at least three days with allopurinol prior to the first dose of AEG35156 and throughout protocol therapy. * Patients must be hydrated with 1 L of normal saline prior AEG35156 infusion
Providence Saint-Joseph Medical Center
Burbank, California, United States
New York Medical College
Valhalla, New York, United States
The Cleveland Clinic, Taussig Cancer Institute
Cleveland, Ohio, United States
Scott and White Memorial Hospital
Temple, Texas, United States
Objective tumor response according to CLL NCI-WG criteria
Time frame: Every numbered cycles
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Tom Baker Cancer Centre
Calgary, Alberta, Canada
Princess Margaret Hospital
Toronto, Ontario, Canada
Jewish General Hospital - Sir Mortimer B. Davis
Montreal, Quebec, Canada