Recent work on the biology of CLL has revealed a role for the tumor microenvironment in promoting leukemia cell survival and resistance to chemotherapy in-vitro, and presumably in-vivo. Revlimid, an immunomodulating agent does not cause direct cytotoxcity to CLL cells in-vitro. However, lenalidomide has been found in early clinical trials to have clinical activity in patients with relapsed CLL. The mechanism for the clinical activity of lenalidomide in CLL is not known, but potentially involves modulating the survival signals provided by the CLL microenvironment.
Dr. James and Dr. Kipps have developed an investigator-initiated multi-center CLL Research Consortium study to evaluate the combination of Revlimid and rituximab for the initial treatment of progressive CLL. The purpose of this study is to determine the response rate of the combination of Revlimid® and Rituximab in previously untreated CLL patients in two arms- those aged 65 years and above and those younger than 65. Secondary objectives will evaluate the safety of the combination of Revlimid® and Rituximab, response duration, safety, and the significance of the tumor flare reaction.
All patients will be assessed for known prognostic factors for CLL as well as novel prognostic factors and will then be evaluated for predicting response to treatment. Biologic corollary studies are designed to evaluate the mechanism of Revlimid® in CLL and the combination of Revlimid® and Rituximab. Recently Dr. Kipps was awarded a R21 grant from the NCI to understand the impact of Revlimid treatment on the CLL microenvironment and to assess whether such knowledge can be used to stratify patients who are most likely to benefit from therapy with lenalidomide in the future. To obtain more information on this clinical study contact - Jamie Gould (858)822-5364
Dr. Kipps has been involved in an international Phase II study and has determined that ofatumumab, a fully humanized anti-CD20 antibody, is effective in patients with chronic lymphocytic leukemia (CLL) who have previously received Rituxan® (rituximab). The details of this study were reported at the 2009 meeting of the American Society of Clinical Oncology.
This study involved 138 patients who were refractory to Fludara and Campath (n=59) or were refractory to Fludara and had bulky disease (n=79). In double-refractory patients the overall response rate was 54% in patients with any prior exposure to Rituxan and 63% in patients who had no prior exposure to Rituxan. Single-agent therapy with ofatumumab is effective in patients with doubly refractory or bulky fludara refractory CLL.
In response to the positive findings ofatumumab came one step closer to gaining approval after an advisory panel recommended the Food and Drug Administration approve the therapy. This agent may be even more effective in combination with other agents. To assess this, we have designed a new phase II study of Ofatumumab in combination with High-dose methylprednisolone (HDMP) for patients with previously treated CLL. To obtain more information on this clinical study contact Shiela Hoff (858)822-5360
The combination of High-dose methylprednisolone (HDMP) and Rituximab for the treatment of CLL and has been pioneered by investigators in the BCRF. This treatment can be administered with little myelotoxicity (bone marrow suppression), is well tolerated including in older individuals over the age of 70, and results in very high response rates even in patients with fludarabine refractory disease. The use of this combination has been investigated for patients who have not received previous treatment using both standard doses of rituximab and high-doses of rituximab. This work was selected for an oral presentation at the American Society of Hematology 50th Annual Meeting ( http://ash.confex.com/ash/2008/webprogram/Paper15428.html ) and is in press at the Journal Leukemia. Currently, the use of high-dose Rituximab with HDMP is being evaluated for the first-line treatment of CLL in an ongoing clinical study at UCSD. To obtain more information on this clinical study contact Shiela Hoff (858)822-5360