Dose-adjusted Chemotherapy for Untreated c-MYC-positive Lymphomas

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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.

Principal Investigator

Dr. Kieron Dunleavy, NCI Center for Cancer Research

Kieron M. Dunleavy, M.D.

Dr. Kieron Dunleavy, Principal Investigator

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.”

For More Information

See the lists of eligibility criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.