EL625 in Persistent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
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)
Lymphoma, Small Lymphocytic
Leukemia, Lymphocytic, Chronic
Drug: cenersen sodium
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of EL625 in Patients in Persistent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma|
- Number of Patients With an Overall Response (Complete Response + Partial Response) [ Time Frame: every 3 cycles ] [ Designated as safety issue: No ]Overall Response is the total number of participants with a Complete (CR) or Partial (PR) response. CR requires the absence of lymphadenopathy, hepatomegaly or splenomegaly and constitutional symptoms and a normal CBC; bone marrow must be at least normocellular for age, with less than 30% nucleated cells being lymphocytes with no lymphoid nodules. Partial Response: requires ≥ 50% decrease in one of the following: peripheral blood lymphocyte count, lymphadenopathy, enlargement of liver and/or spleen, or bone marrow involvement by CLL AND at least one hematologic parameter met for 2 months.
- Progression Free Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]Progression is defined as at least one of the following: 1) ≥ 50% increase in the sum of the products of at least two lymph nodes one two consecutive determinations (at least one node must be ≥ 2 cm); appearance of new palpable lymph nodes, 2) ≥ 50% increase in the size of the liver and/or spleen; appearance of palpable hepatomegaly or splenomegaly, which was not previously present, 3) ≥ 50% increase in the absolute number of circulating lymphocytes to at least 5,000/µl or 4)Transformation to a more aggressive histology.
- Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2008|
|Study Completion Date:||May 2012|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Experimental: all patients
EL625 combined with traditional chemotherapy (rituximab, fludarabine, and cyclophosphamide)
Drug: cenersen sodium
2.4 mg/kg/day as a continuous infusion over 24 hours starting on day one and ending on day 4
Other Name: EL625Drug: Rituximab
375 mg/m2 on day 2
Other Name: RituxanDrug: Cyclophosphamide
250 mg/m2 on days 2, 3, and 4
Other Name: CytoxanDrug: Fludarabine
25 mg/m2 on days 2, 3, and 4
Other Name: Fludara
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.
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||David Rizzieri, MD||Duke University|