With funding from the Lymphoma Research Foundation, a new clinical trial recently opened for newly diagnosed mantle cell lymphoma (MCL) patients. The trial will study the effectiveness of a new vaccine created from patients' own cancer cells and a follow up procedure where the patient’s immune system is essentially reset. The trial, led by Ronald Levy, MD and Joshua Brody, MD in the Division of Oncology at Stanford University, has already enrolled eight participants and is the direct result of a 2007 Clinical Investigator Career Development Award from LRF to study cancer vaccines as a way to eliminate residual lymphoma and significantly improve cancer-free survival among patients with MCL. Today’s standard treatment for MCL – chemotherapy and an autologous stem cell transplant, where the transplanted stem cells come from the patients own body – kills most of the cancer said Dr. Brody. The goal of this trial is to eliminate the remaining few cancer cells that do not respond to chemotherapy.   Josh Brody, MD 

"Standard therapies get rid of 99.9 percent of the cancer but the last .1 percent has to be attacked in a different way," Brody said. "Even though these remaining cancer cells might be chemo-resistant we have reason to believe they will not be immune resistant."

The process of treatment in the clinical trial is described by the investigators as follows. Prior to the start of therapy, cancer cells are extracted from the patient either by biopsy or pheresis, a process by which blood is filtered and the cells desired are separated and removed. The cancer vaccine is created in the lab by combining that sample with an immunostimulant, an agent that stimulates an immune response. The patient is given standard chemotherapy – either at Stanford or with their local oncologist – and after patients achieve a temporary remission, they are treated with the vaccine to induce an anti-cancer immune response. Doctors then "harvest" the patient’s immune system by pheresis, patients proceed to standard autologous stem cell transplant, and immediately afterwards are re-infused with their anticancer immune system – a process termed 'immunotransplant." At this point the patient’s immune system is essentially a "blank page," and – boosted by additional vaccines – re-grows and "anti-cancer immune cells proliferate, grow and become more effective."

Vaccines have been studied in other cancers, but the Stanford trial is different because of the addition of the immunostimulant to the vaccine and the immunotransplant process. He hopes that this model will be a success and would like to see it applied first to other lymphomas and then to other solid cancers of potentially the breast or prostate.

"We have the capability to eradicate minimal residual disease that persists after transplants, and prolong patients’ lives even more," Brody said. "I am optimistic because in animal models, this maneuver was able to cure extremely advanced cancers."

The study opened in August 2009 and plans to treat 30 patients over several years, the first patients having received vaccine in October 2009. Anticipating the likely timeline for study results, for patients undergoing only chemotherapy, cancer can return within two years. If a stem cell transplant is added to treatment, the cancer can return in three to four years and researchers must wait a while to tell if the novel therapy was truly effective in prolonging those cancer-free intervals. During the course of this study, Drs. Levy and Brody will be able to measure anti-cancer immune responses in the patients’ blood. Therefore, within several weeks after the vaccine and immunotransplant, they may have some evidence of whether the therapy was successful.

"LRF believed in us a long time ago when this was just an idea and they saw it as a good idea," Brody said. "If it were not for the Foundation’s funding and their openness to new approaches this study never could have been developed. We have been fortunate to receive interest from patients and their families from across the country and we hope that the study’s results will be worthy of all the support we have received."

To view the details of the clinical trial listed on the MCLC Clinical Trials Database, click here.

November 2, 2009