Lymphoma -- Clinical Research Program

Lymphomas are divided into two groups: Hodgkin’s disease and non-Hodgkin lymphoma. All lymphomas are diseases of the lymphatic tissue.

Our lymphoma research group has an active drug-development program, focusing on molecular targets and other new agents for patients whose disease has progressed and is nonresponsive to standard treatments. Our clinical trials are evaluating immunotherapies as well as small-molecule drugs that target specific intracellular pathways. We are at the forefront of developing treatments that combine multiple treatment modalities, including chemotherapy, immunotherapy, radioimmunotherapy, and radiation therapy.

Among our recent research accomplishments:

Molecular Pathology

  • A microarray study of tissue from lymphoma patients showed that pretreatment levels of the p27 protein correlate with response to bortezomib. (Bortezomib, a proteasome inhibitor, is approved for the treatment of multiple myeloma after prior treatments have failed.) In addition, pretreatment levels of p27, Bcl-6, and p65 correlate with progression-free survival in this patient group.

New Agents

  • A trial identified significant single agent activity of the proteasome inhibitor bortezomib in the treatment of mantle cell lymphoma (MCL) and follicular lymphoma. Along with data from other centers, these results led to a national study of bortezomib for treatment of MCL and to Food and Drug Administration approval of bortezomib for relapsed and refractory MCL. J Clin Oncol. 2005 Feb 1;23(4):676-84. [PubMed Abstract]; Clin Lymphoma Myeloma. 2005 Nov;6(3):191-9. [PubMed Abstract]
  • We have a phase I/II trial looking at combining bortezomib with rituximab, cyclophosphamide, and prednisone. Two sequential phase I components have been completed with two-dose schedules of bortezomib, and the phase II dose has been determined. The phase I studies showed promising efficacy.
  • A phase I/II study of pralatrexate, a novel antimetabolite developed at Memorial Sloan Kettering, has demonstrated single-agent activity in a wide range of T cell malignancies. Allos Therapeutics has licensed pralatrexate from us and has recently completed a multicenter trial to confirm our results, reporting a 29 percent response rate. In addition, pralatrexate is being evaluated in patients with non-small cell lung cancer, bladder cancer, and a range of lymphoma subtypes. Curr Opin Oncol. 2006 Nov; 18(6):591-7. [PubMed Abstract]
  • We are leading a multicenter phase I/II trial evaluating the use of pralatrexate and gemcitabine with B12 and folic acid to treat relapsed/refractory lymphoproliferative malignancies.

Immunotherapy

  • Members of our team did a retrospective analysis of rituximab maintenance following high-dose therapy with autologous stem cell transplantation for relapsed or primary refractory diffuse large B cell lymphoma. The results suggested a strong survival advantage for the patient group receiving rituximab after high-dose therapy with stem cell transplantation. However, this advantage was not found to be true for patients with mantle cell lymphoma.
  • We led a multicenter phase III trial to evaluate an immunotherapeutic approach in follicular lymphoma consisting of passive immunotherapy with rituximab followed by active immunization with a patient-specific vaccine (mitumprotimut-T and granulocyte-macrophage colony-stimulating factor). The results suggested this approach made no difference in progression-free survival compared with placebo. J Clin Oncol. 2009 May 4. [Epub ahead of print] [PubMed Abstract]
  • One of our investigators is leading a phase I trial testing a novel vaccine strategy against B cell lymphoma by targeting CD20, a protein found on the surface of most lymphoma cells. The approach involves injecting patients with a fragment of DNA that contains the gene for the CD20 protein. The DNA contains a short part of the mouse CD20 gene and makes a short, altered form of CD20, which the body recognizes as foreign and thus mounts an immune response against.

Drug Combinations and Multimodal Treatments

  • We are leading an effort to develop an oncogeriatric program for lymphoma, developing risk-adapted treatment strategies for elderly patients with aggressive non-Hodgkin lymphoma. A clinical trial program is being developed for elderly nontransplant patients with diffuse, large B cell lymphoma, with the goal of incorporating oncogeriatric assessments in order to potentially risk-stratify patients.
  • We are leading a phase II trial to evaluate the safety and effectiveness of an investigational drug called depsipeptide in patients with peripheral T cell lymphoma that has returned despite prior chemotherapy or has not responded to standard therapies.
  • Members of our group are leading a study evaluating the effectiveness of using doxorubicin followed by bexarotene against advanced-stage cutaneous T cell lymphomas.
  • We are leading a phase I/II trial to replace procarbazine, a drug with many side effects, with a new drug, vorinostat, in a drug combination for the treatment of elderly patients with relapsed diffuse large B cell lymphoma (DLBCL). Vorinostat, a drug called a histone deacetylase inhibitor, is approved for the treatment of certain lymphomas of the skin.
  • Several members of the Lymphoma Service have been active in the AIDS Malignancy Consortium. One of our members is national principal investigator on a phase II study of a high-dose, short-course regimen called CODOX-M/IVAC in patients with previously untreated HIV-associated or atypical Burkitt lymphoma. The treatment combines the chemotherapy drugs rituximab (R), cyclophosphamide (C), vincristine (O), doxorubicin (DOX, also known as Adriamycin), methotrexate (M), ifosfamide (I), etoposide (V, also known as VP-16), and cytarabine (AC). This is already one of the standard treatments for patients with Burkitt lymphoma who do not have HIV infection. The treatment regimen also includes chemotherapy administered to the spinal fluid, which is always assessed for cancer cells. In this study, investigators will also examine patients’ spinal fluid with a protein test to see if that method is more sensitive than routine testing.
  • We are also participating in a phase II trial to evaluate the effectiveness of giving liposomal doxorubicin (doxorubicin enclosed in a fat capsule) in combination with the drugs rituximab, cyclophosphamide, vincristine, and prednisone (a regimen called DR-COP) to patients with B cell non-Hodgkin lymphoma and HIV infection.
  • We are leading a clinical trial to see if treatment with the antibiotic clarithromycin (Biaxin), given by mouth for three months, can shrink or delay the growth of newly diagnosed indolent lymphoma not requiring treatment.
  • One of our team members is a co-principal investigator on a national phase III trial comparing a chemotherapy regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) against a regimen of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) in patients with previously untreated de novo diffuse large B cell non-Hodgkin lymphoma. In addition to the planned clinical endpoints, the study is a prospective evaluation of gene expression profiling for the prognostication of diffuse large B cell lymphoma (DLBCL) and determination if there are regimen-specific pathways predictive of outcome.
  • For relapsed or refractory diffuse large B cell lymphomas, we participated in the international randomized Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) study, which was based on our study using the chemotherapy regimen of rituximab-ifosfamide-carboplatin-etoposide (RICE).