A Phase 1-2, Multicenter, Open-Label Study of AEG35156 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Indolent B-Cell Lymphomas - NCT00768339-44195(Clinical Trial 245245)
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| City: |
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Cleveland |
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State:
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OH |
| Zip Code: |
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44195 |
| Conditions: |
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Leukemia, Lymphocytic, Chronic, B-Cell - Lymphoma, B-Cell |
| Purpose: |
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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.
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| Study summary: |
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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. |
| Criteria: |
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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 |
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| Study is available at: |
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The Cleveland Clinic, Taussig Cancer Institute
Cleveland, OH 44195
United States
Primary Contact:
John Sweetenham, MD
Phone: 216-445-6707 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 22, 2011 |
Modifications to
this listing: |
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above to view all information about this clinical trial. |
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