Genasense® (Oblimersen Sodium), Fludarabine, and Rituximab in Subjects With Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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The treatment combination of Rituxan® (rituximab) and fludarabine has previously been reported to produce a high percentage of responses with less toxicity than other combination treatments. However, some leukemia subjects continue to have leukemia despite treatment with these standard anticancer drug therapies, or they may work for only a short period of time. In some subjects, when the leukemia does not respond well to therapy the leukemia cells may be over-producing one or more proteins. One of these proteins is called Bcl-2. Bcl-2 is a protein that appears to protect cancer cells from being killed and thus lengthens the life of the cancer cells. Genasense® (oblimersen sodium) is a compound that blocks production of the Bcl-2 protein. By first lowering levels of Bcl-2, it is possible that chemotherapy drugs may work more effectively as a cancer treatment. Genasense® may also directly kill CLL cells. This study will test whether treating subjects with Genasense®, fludarabine and rituximab is safe and effective.

Official Title
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A Pilot Study of Genasense® (G3139, Oblimersen Sodium, Bcl-2 Antisense Oligonucleotide), Fludarabine and Rituximab in Previously Treated Subjects With Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Oblimersen-rituximab-fludarabine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Absolute lymphocyte count of > 10,000 cells/mm3 or history of ALC >10,000 cell/mm3 Platelets > 50,000 cells/mm3 Tumor lymphocytes expressing surface CD5, CD19, CD20 and CD23 Creatinine < 1.5 mg.dL Key Exclusion Criteria: Less than 3 weeks from any prior major surgery or other therapy for CLL including radiation therapy, chemotherapy, high-dose steroid therapy, immunotherapy, cytokine, biologic or vaccine therapy. History of autoimmune hemolytic anemia Prior allogeneic transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Oblimersen-rituximab-fludarabine|28-day cycles; Cycle 1: oblimersen by continuous IV infusion 1.5 mg/kg/d for 7 consecutive days, completing on Day 8; rituximab by IV infusion on Day 4 (125 mg/m2) and Day 6 (250 mg/m2); fludarabine 25 mg/m2 by IV infusion for 3 days, starting on Day 6. Subsequent cycles: oblimersen 3 mg/kg/d, completing on Day 8; rituximab 375 mg/m2 on Day 5; fludarabine 25 mg/m2 for 3 days starting the same day as rituximab|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and complete response rate |  | Monthly for response | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, Leukemia, Chronic, Cancer, Adult, Lymphocytic, Genasense, G3139, Genta, Bcl-2, Antisense, Oligonucleotide, oblimersen