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

NCT00768339 | Terminated Phase 1

• 1 other identifier: AEG35156-204
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell

Keywords

antisense; AEG35156; lymphocytic; lymphoma; leukemia; B-cell

Outcome Measures

Primary Outcomes (1)

• Objective tumor response according to CLL NCI-WG criteria

  Every numbered cycles

Study Arms (1)

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

Interventions

AEG35156 antisense IV infusion DRUG

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

Also known as: XIAP antisense

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aegera Therapeutics: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (7)

Providence Saint-Joseph Medical Center

Burbank, California, 91505, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

The Cleveland Clinic, Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

Scott and White Memorial Hospital

Temple, Texas, 76508, United States

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital - Sir Mortimer B. Davis

Montreal, Quebec, H3T 1E2, Canada

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Lymphoma; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin

Study Officials

• John Sweetenham, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 6, 2008
• First Posted: October 8, 2008
• Study Start: September 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: September 1, 2011
• Last Updated: July 13, 2011

Record last verified: 2011-07

Locations

US (4); CA (3)