Conditions: Lymphoma, Small Lymphocytic Leukemia, Lymphocytic, Chronic
Keywords: Small Lymphocytic Lymphoma Chronic Lymphocytic Leukemia EL625 cenersen
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 20
Healthy volunteers: no

Brief summary:
The purpose of this research study is to see if the investigational drug EL625, when combined with traditional chemotherapy (rituximab, fludarabine, and cyclophosphamide), is effective in Persistent Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

Detailed description:
Chronic lymphocytic leukemia (CLL) and small B-cell lymphocytic lymphoma (SLL) are thought to be different manifestations of the same disease. Treatment options for CLL/SLL range from a watch and wait approach to bone marrow transplant. Currently there is no consensus on the best treatment regimen and new approaches to treatment are needed.

EL625 is a 20-mer antisense molecule which binds to a coding region of exon 10 in p53 RNA transcripts. It can bind to both mutant and wild type p53. p53 is involved in regulating apoptosis and DNA repair in cells. When genetic damage occurs p53 is upregulated. As the expression of p53 increases in normal cells they are more likely to undergo apoptosis rather than cell cycle arrest and DNA repair. However in malignant cells, for a given level of DNA damage they are more likely to undergo cell cycle arrest and repair rather than apoptosis. Because EL625 is theorized to increase response to chemotherapy, we propose adding EL625 to a combination of fludarabine, cyclophosphamide and rituximab.

Arms:
arm 1: EL625 combined with traditional chemotherapy (rituximab, fludarabine, and cyclophosphamide)

Interventions: intervention 1: cenersen sodium intervention 2: Rituximab intervention 3: Cyclophosphamide intervention 4: Fludarabine
Intervention descriptions: intervention 1: 2.4 mg/kg/day as a continuous infusion over 24 hours starting on day one and ending on day 4 intervention 2: 375 mg/m2 on day 2 intervention 3: 250 mg/m2 on days 2, 3, and 4 intervention 4: 25 mg/m2 on days 2, 3, and 4

Protocol document: