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| Sponsor: | Aegera Therapeutics |
|---|---|
| Collaborator: |
The Leukemia and Lymphoma Society |
| Information provided by: | Aegera Therapeutics |
| ClinicalTrials.gov Identifier: | NCT00768339 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, B-Cell |
Drug: AEG35156 antisense IV infusion |
Phase I Phase II |
| Study Type: | Interventional |
| Study Design: | Treatment, Open Label, Historical Control, Single Group Assignment, Efficacy Study |
| Official Title: | AEG35156-204: A Phase 1-2, Multicenter, Open-Label Study of the X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Indolent B-Cell Lymphomas |
| Estimated Enrollment: | 24 |
| Study Start Date: | September 2008 |
| Estimated Study Completion Date: | September 2010 |
| Estimated Primary Completion Date: | August 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
1: Experimental
Single agent AEG35156 as 2hr IV infusion, weekly dosing in Patients with relapsed or refractory chronic lymphocytic leukemia and indolent B-cell lymphomas
|
Drug: AEG35156 antisense IV infusion
AEG35156 will be given as a 2-hour intravenous infusion (escalating dose 50, 100, 150, 200 mg) once weekly on Day 1, Day 8 and Day 15. One cycle of therapy will consist of 21 days.
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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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| United States, Ohio | |
| The Cleveland Clinic, Taussig Cancer Institute | Not yet recruiting |
| Cleveland, Ohio, United States, 44195 | |
| Contact: John Sweetenham, MD 216-445-6707 | |
| Principal Investigator: John Sweetenham, MD | |
| Canada, Alberta | |
| Tom Baker Cancer Centre | Recruiting |
| Calgary, Alberta, Canada, T2N 4N2 | |
| Contact: Nizar J Bahlis, MD 403-944-1564 nizarbah@cancerboard.ab.ca | |
| Contact: Kelly Mclachlan 403-521-3520 kellymcl@cancerboard.ab.ca | |
| Principal Investigator: Nizar J Bahlis, MD | |
| Canada, Ontario | |
| Princess Margaret Hospital | Recruiting |
| Toronto, Ontario, Canada, M5G 2M9 | |
| Contact: Christine Chen, MD christine.chen@uhn.on.ca | |
| Sub-Investigator: Aaron Schimmer, MD | |
| Sub-Investigator: John Brandwein, MD | |
| Principal Investigator: Christine Chen, MD | |
| Principal Investigator: | Christine Chen, MD | Princess Margaret Hospital, Canada |
More Information
| Responsible Party: | Aegera Therapeutics Inc ( Jacques Jolivet, MD, Senior VP Clinical ) |
| Study ID Numbers: | AEG35156-204 |
| Study First Received: | October 6, 2008 |
| Last Updated: | February 5, 2010 |
| ClinicalTrials.gov Identifier: | NCT00768339 History of Changes |
| Health Authority: | United States: Food and Drug Administration; Canada: Health Canada |
|
antisense AEG35156 lymphocytic |
lymphoma leukemia B-cell |
|
Leukemia, Lymphoid Neoplasms by Histologic Type Immunoproliferative Disorders Immune System Diseases Lymphoma, B-Cell Leukemia Lymphatic Diseases |
Neoplasms Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, B-Cell Lymphoproliferative Disorders Lymphoma, Non-Hodgkin Lymphoma |