A Phase 1-2, Multicenter, Open-Label Study of AEG35156 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Indolent B-Cell Lymphomas - Full Text View

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:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Acute Lymphocytic Leukemia Cancer Chronic Lymphocytic Leukemia Leukemia Lymphoma

U.S. FDA Resources

Further study details as provided by Aegera Therapeutics:

Primary Outcome Measures:

Objective tumor response according to CLL NCI-WG criteria [ Time Frame: Every numbered cycles ] [ Designated as safety issue: No ]

Enrollment:	25
Study Start Date:	September 2008
Estimated Study Completion Date:	September 2011
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 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, 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 Other Name: XIAP antisense

Arms

Assigned Interventions

Experimental: 1

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, 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

Other Name: XIAP antisense

Detailed Description:

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

Criteria

Inclusion Criteria:

Patients with an histologically confirmed diagnosis of CLL as per NCI-WG criteria or
Patients with an histologically confirmed diagnosis of one of the following indolent B-cell lymphomas: (Follicular lymphoma (FL); Small lymphocytic lymphoma (SLL); Marginal zone lymphoma; Lymphoplasmacytic lymphoma)
Relapsed or refractory patients who have failed at least 2 prior lines of therapy, one of which may have been high dose therapy and autologous stem cell transplantation. Steroids alone when used for autoimmune phenomena do not qualify as prior therapy
ECOG performance less or equal than 2
Life expectancy of at least 3 months
Age greater or equal than 18 years
Signed, written IRB-approved informed consent
A negative serum pregnancy test (if applicable)
Acceptable liver function:(Bilirubin within normal limit; AST (SGOT) and ALT (SGPT) less or equal than 2.5 x ULN or less or equal than 5 x ULN if there are liver lymphomatous involvement)
Acceptable renal function: (Serum creatinine within normal limits, OR calculated creatinine clearance greater or equal than 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal)
Acceptable hematologic status: (Granulocyte greater or equal than 1000 cells/uL; Platelet count greater or equal than 50,000 /uL)
Acceptable coagulation status:(PT within normal limits; PTT within normal limits)
For women of child-producing potential, the use of effective contraceptive methods during the study
Prior radiotherapy for local disease is allowed provided disease progression has been documented, and treatment completed at least 4 weeks prior to registration

Exclusion Criteria:

Uncontrolled autoimmune hemolysis and/or thrombocytopenia
Richter's transformation
Histologic transformation
Patients with peripheral neuropathy
Active progressive leptomeningeal disease including the presence of any related symptoms or need for corticosteroids. A CT or MRI scan of the head is necessary in patients with a history of leptomeningeal disease to document the stability of prior lesions
Pregnant or nursing women. NOTE: Women of child-bearing potential must agree to use adequate contraception (sterile or surgically sterile; hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Men who are unwilling to use acceptable forms of birth control when engaging in sexual contact with women of child bearing potential
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
Known infection with HIV, hepatitis B, or hepatitis C
Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
Patients who are currently receiving any other investigational agent. Subjects who have used a previous antisense oligonucleotide in the last 90 days will be excluded
Unwillingness or inability to comply with procedures required in this protocol

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768339

Locations

United States, California
Providence Saint-Joseph Medical Center
Burbank, California, United States, 91505
United States, New York
New York Medical College
Valhalla, New York, United States, 10595
United States, Ohio
The Cleveland Clinic, Taussig Cancer Institute
Cleveland, Ohio, United States, 44195
United States, Texas
Scott and White Memorial Hospital
Temple, Texas, United States, 76508
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital - Sir Mortimer B. Davis
Montreal, Quebec, Canada, H3T 1E2

Sponsors and Collaborators

Aegera Therapeutics

The Leukemia and Lymphoma Society

Investigators

Principal Investigator:

John Sweetenham, MD

The Cleveland Clinic

More Information

No publications provided

Responsible Party:	Jacques Jolivet, MD, Senior VP Clinical, Aegera Therapeutics Inc
ClinicalTrials.gov Identifier:	NCT00768339 History of Changes
Other Study ID Numbers:	AEG35156-204
Study First Received:	October 6, 2008
Last Updated:	July 12, 2011
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada

Keywords provided by Aegera Therapeutics:

antisense
AEG35156
lymphocytic

lymphoma
leukemia
B-cell

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms

Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on February 13, 2012