Dose-adjusted Chemotherapy for Untreated c-MYC-positive Lymphomas
Name of the Trial
Phase II Study of Dose-Adjusted EPOCH-Rituximab in Adults with Untreated Burkitt Lymphoma and c-MYC+ Diffuse Large B-Cell Lymphoma (NCI-10-C-0052). See the protocol summary.
Dr. Kieron Dunleavy, NCI Center for Cancer Research
Why This Trial Is Important
Burkitt lymphoma is an aggressive type of non-Hodgkin lymphoma (NHL) that often affects children and young adults. People infected with HIV are much more likely to develop Burkitt lymphoma than those who are HIV negative. A defining feature of this cancer is a chromosome change that causes increased expression of a gene called c-MYC, which encodes a protein that helps turn other genes on and off. The c-MYC gene is also abnormally active in some patients with diffuse large B-cell lymphoma (DLBCL), the most common type of NHL. Overexpression of c-MYC (known as c-MYC positivity) in these cancers is associated with a very high rate of cell proliferation.
Burkitt lymphoma can be successfully treated with a complex regimen of chemotherapy, but this treatment is often associated with a high rate of complications, especially among older patients and patients whose immune system is suppressed. In addition, patients with c-MYC-positive DLBCL tend to fare poorly with standard treatment compared with those who have c-MYC-negative disease. A chemotherapy regimen developed at NCI called EPOCH in combination with an antibody called rituximab (the EPOCH-R regimen) has been shown to help improve the outcomes of patients with some forms of aggressive NHL.
EPOCH-R appears to be particularly active against B-cell lymphomas that have high cell proliferation rates, so NCI researchers conducted a study of this regimen, with the doses of some of the drugs adjusted in each treatment cycle to achieve optimum concentrations (dose-adjusted EPOCH-R), in patients with previously untreated Burkitt lymphoma. All 30 patients in the study experienced complete remission. Now, the researchers are conducting a larger study of this treatment for patients with untreated Burkitt lymphoma to confirm the earlier results and are extending the treatment to patients with c-MYC-positive DLBCL to see if those patients will also benefit from dose-adjusted EPOCH-R therapy.
In this trial, adult patients with newly diagnosed Burkitt lymphoma or c-MYC-positive DLBCL will be separated into low-risk and high-risk groups depending on their clinical characteristics and prognostic factors. Those in the low-risk group will be treated with at least three cycles of chemotherapy, while those in the high-risk group will receive six cycles. Patients with c-MYC-positive plasmablastic lymphoma (a very rare subtype of DLBCL characterized by the absence of CD20, the protein targeted by rituximab) will be treated with dose-adjusted EPOCH but not rituximab. Doctors will assess the safety and effectiveness of dose-adjusted EPOCH or EPOCH-R in these patients.
“We initiated this study for a couple of reasons,” said Dr. Dunleavy. “Firstly, moving on from our previous experience using dose-adjusted EPOCH-R in Burkitt lymphoma, we wanted to stratify patients into low-risk and high-risk groups and minimize the number of treatment cycles for patients with low-risk disease. Secondly, we wanted to investigate this therapeutic strategy in a multicenter study, and, thirdly, given the fact that c-MYC-positive diffuse large B-cell lymphoma has a poor outcome with standard therapy, we wanted to prospectively evaluate this therapy in that group of patients.”