Archive for the ‘Lymphoma’ Category

Bendamustine (Treanda) Approved for Treatment of Lymphoma

December 10, 2008

Low-grade follicular B-cell lymphoma is diagnosed in 30,000 US patients each year.  The disease is most often diagnosed at an advanced stage, and there is no know curative treatment in such patients.  Older therapy, which included alkylators such as cyclophosphamide, produces response and remissions.  Cyclophosphamide is often given in combination with other drugs such as vincristine (Oncovin) and prednisone, known as the CVP regimen.   Rituximab (Rituxan), is a monoclonal anti-CD20 antibody. CD20 is present on mature B-cells, including low-grade lymphoma.  Rituximab therapy is now extensive used alone or in combination with chemotherapy for treatment of low-grade B-cell lymphoma.  It is FDA-approved in combination with CVP (R-CVP), following CVP as monotherapy “maintanance”, or at relapse.  The use of first-line Rituximab-chemotherapy combinations such was R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) has been reported to produce response in 97%, with prolonged remission (median progression-free survival=50 months) (Hiddeman, Blood, 2003).  

Relapsed patients have somewhat less responsive disease, and remissions are not expected to be as durable.  

Bendamustine (Treanda) received FDA-approval for treatment of relapsed B-cell follicular low-grade non-Hodgkin’s lymphoma on 11/3/08.  The approval was based on studies demonstrating a high response rate (74%) and long progression-free duration (median 9.3 months) in patient who received bendamustine therapy for relapse of their disease during or within 6 months of a prior rituximab (Rituxan)-containing treatment regimen.   This approval comes within one year of the drug’s initial approval for treatment of chronic lymphocytic leukemia (CLL), another indolent B-cell neoplasm. 

The addition of rituximab to bendamustine therapy (R-Treanda) has been studied in a phase II study, producing response in 92% of patients (41% complete responses), with median progression-free survival of 23 months.  (Robinson, Journal of Clinical Oncology, 2008).  

In addition to offering our patients bendamustine therapy as an option for management, CORT is conducting a trial of rituximab +/- galiximab (anti-CD80 monoclonal antibody).  This study will test whether dual antibody therapy improves outcome compared to rituximab alone, for relapsed, but rituximab-sensitive disease. 

For more information about bendamustine (Treanda) therapy or lymphoma therapy options at CORT, contact a Clinical Care Coordinator at 972-566-5588, or visit our website at www.CORTPA.com.

Galiximab for Low-Grade B-cell Lymphoma

October 3, 2007

CD80 (B7.1) is a membrane-bound molecule that is known for its role in regulating immune T-cell activity. Several studies have suggested that CD80 may also play a role in the regulation of normal and malignant B cells. CD80 is continuously expressed on a variety of lymphomas, including low grade B-cell lymphoma, making it an attractive target for lymphoma therapy. In lab studies, cross linking CD80 with anti-CD80 antibodies on lymphoma cells has been shown to inhibit cell proliferation, to induce cell death regulating (pro-apoptotic) molecules, and to induce antibody-dependent cell mediated cytotoxicity (ADCC). These observations constitute the rationale for development of an anti-CD80 therapy for B-cell lymphoma. Galiximab is a monoclonal antibody that binds and inhibits CD80. In a phase II study of single-agent galiximab in refractory low grade B-cell lymphoma, 11% of patients had response, with two complete responses. The most common side effects were fatigue, nausea, and headache. Low blood counts were rare.

The TARGET NHL Trial (Targeted Antibody Therapy with RITUXAN and Galiximab Efficacy Trial), continuing enrollment at CORT, is a randomized, double-blind, global multi-center study (114-NH-301) of galiximab in combination with rituximab compared with rituximab in combination with placebo. The primary study objective is to compare the clinical benefit of each treatment arm in subjects with relapsed or refractory, follicular NHL. Progression-free survival (PFS) is the primary study endpoint. An open-label retreatment study (114-NH-302) with galiximab in combination with rituximab, will be available to subjects who progress on 114-NH-301 after experiencing at least a partial response (PR) with a time to progression (TTP) of six months or greater in either arm of the study.


For more information on these studies, visit www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588.

Anti-Angiogenic Therapy in Testing for Diffuse Large B-Cell Lymphoma

October 3, 2007

Bevacizumab (Avastin) is a new agent that “targets” tumor blood vessels by the inhibition of VEGF (vascular endothelial growth factor). It has been tested in combination with chemotherapy in a variety of tumor types, with significant improvements in survival, leading to approval of Avastin in the treatment of colon cancer, and general practice use for treatment of breast and lung cancer.

Avastin is being tested in the treatment of advanced stage diffuse large B-cell lymphoma in a study at CORT. The study compares standard treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) to R-CHOP plus Avastin. The goal of the study is to determine if the addition of Avastin improves the cure rate and survival after treatment.

The risks of treatment with standard therapy include fever, infection, hair loss, nausea, vomiting, mouth sores, low blood counts, fatigue, sensory nerve injury, and cardiac dysfunction. The risks of Avastin include high blood pressure, protein in the urine, infusion reactions, allergy, bleeding, blood clots, and rare central nervous system vascular injury or bowel perforations. Most Avastin risks are mild-moderate, and tolerable.

For more information on these studies, visit www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588.

Belinostat (PXD101) for Refractory Aggressive Lymphoma: A Novel New Drug

October 3, 2007

Belinostat (PXD101) is a promising small molecule histone deacetylase (HDAC) inhibitor being investigated for its role in the treatment of a wide range of solid and hematologic malignancies either as a single-agent, or in combination with other active anti-cancer agents. HDAC inhibitors represent a new class of anti-cancer therapeutics that target HDAC enzymes and have been shown to arrest growth of cancer cells (including drug resistant subtypes), induce cell death, inhibit angiogenesis; and sensitize cancer cells to overcome drug resistance when used in combination with other anti-cancer agents.


Intravenous belinostat is currently being evaluated in the SWOG S0520 Study at CORT for treatment of refractory aggressive B-cell lymphoma, including large cell lymphoma, Burkitt’s-like lymphoma, and primary mediastinal lymphoma. Patients may have had up to three prior treatment regimens. Risks of belinostat include rash, edema, constipation, low platelet blood count, fatigue, and dehydration. A potential for changes in the electrocardiogram or arrhythmia exists for this class of drugs.

For more information on these studies, visit www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588.