A Phase II Study of EL625 in Patients in Persistent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Patients With an Overall Response (Complete Response + Partial Response)
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.
every 3 cycles
David Rizzieri, MD
United States: Food and Drug Administration
|Duke University Medical Center||Durham, North Carolina 27710|