John Leonard, M.D.

Associate Professor of Medicine, Weill Medical College of Cornell University; Clinical Director, New York-Cornell Center for Lymphoma and Myeloma in New York City; member of the Mantle Cell Lymphoma Consortium (MCLC) Executive Committee; and co-chair of the MCLC Clinical Trials Working Group

John Leonard, M.D., was drawn to the field of hematology/oncology after he finished his medical training ten years ago because, he says, it offered him the best opportunity to make the greatest impact in patient care. "I enjoy the broad nature of this specialty. It encompasses a set of diseases where we've made a great deal of progress and over the coming years, I think there's going to be a tremendous number of new developments with respect to better treatments," says Dr. Leonard.

That accelerated pace has already begun. Research in angiogenesis and anti-angiogenesis therapy by Dr. Leonard and his collaborators has focused on using low doses of chemotherapy agents given "metronomically" or continuously to treat various lymphomas. Their studies have demonstrated exciting results and they are hopeful that this and other work may ultimately reduce the need for more intensive, higher-dose treatments. "There's a lot of evidence accumulating that angiogenesis may be very important in cancer in general and in lymphoma in particular," says Dr. Leonard. "We are working on trying to understand the biology of angiogenesis and the importance of blood vessel formation in the development and progression of lymphoma. Several years ago, one of my colleagues, Dr. Morton Coleman, developed a low-dose oral chemotherapy regimen to treat various types of lymphoma, primarily for patients who were not appropriate candidates for more intensive regimens. When we went back and reviewed the results, it turned out that this regimen was very active and well tolerated in mantle cell lymphoma in particular."

The treatment regimen called PEP-C, which consists of low-dose oral combinations of prednisone, cyclophosphamide, etoposide and procarbazine given on a daily, alternating day or weekly basis, depending on patient tolerance, may be working through the ability of low doses of chemotherapy to interfere with blood vessel formation in tumors. Dr. Leonard's colleague, Dr. Jia Ruan, is studying this aspect of mantle cell lymphoma biology in samples from patients as well as in laboratory-based models. The group is now conducting a study of relapsed mantle cell lymphoma patients using a newer modified treatment protocol called RT-PEP-C, which includes the addition of Rituxan and thalidomide to PEP-C.

"There were interesting data showing that Rituxan and thalidomide could be useful in mantle cell lymphoma and thalidomide also has anti-angiogenic effects, so we decided to develop this combination treatment program and use it to further study the biology of mantle cell lymphoma with respect to angiogenesis and blood vessel formation," says Dr. Leonard. With several trial participants doing well on the RT-PEP-C regimen as long as two years after starting therapy, Dr. Leonard says the protocol might be considered for use as front-line treatment in the future.

"Ultimately, we envision RT-PEP-C to be a regimen that could be used in some patients as initial treatment and part of its appeal is that it can be a low-dose oral maintenance treatment as opposed to blasting away with chemotherapy," says Dr. Leonard. Besides being effective, the low-dose protocol has the added advantage of being well tolerated by patients. "Most of our patients are able to go to work and conduct their normal everyday activities," says Dr. Leonard. Longer follow-up with larger numbers of patients will be important to determine the regimen's long-term efficacy and the clinical trial remains open to additional patients.

How Clinical Trials Help Patients Win

According to Dr. Leonard, patient participation in clinical trials is critically important to treatment advances, especially in rare cancers. "Because mantle cell lymphoma as well as other subtypes of lymphoma are such uncommon diseases, small clinical trials with small numbers of patients can make a huge impact. And every patient matters from the standpoint of the information that can be learned about the disease as well as the opportunity that a trial presents to provide patients with new options for therapy that can potentially provide substantial benefit", says Dr. Leonard.

To find information about clinical trials, click here.