Phase I Trial With Cohort Expansion of Pentostatin, Bendamustine and Ofatumumab (PBO) for the Treatment of Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States.
There has been considerable progress in understanding the biology and treatment of CLL in
the last 20 years. However, even with modern therapies, complete responses (CR) are
achieved in approximately 25% of the patients with relapsed/refractory disease. Multiple
studies have demonstrated that patients who achieve CR have better clinical outcomes than
patients who do not achieve a CR with therapy. B-cell NHL is composed of multiple subtypes
of neoplasm. These diseases are closely related to CLL in terms of natural history,
biology, and responsiveness to similar therapeutic agents. These diseases are not usually
cured by available chemotherapy and ultimately patients succumb to progression of resistant
disease. Therefore, there is a need to develop better therapies to improve survival in
patients with CLL and B-cell NHL.
Preclinical and clinical data suggests that pentostatin, bendamustine, ofatumumab are active
drugs for the treatment of B-cell malignancies. In an earlier clinical trial conducted by
Dr. Weiss (lead site PI), the combination of pentostatin and cyclophosphamide had very good
activity in previously treated patients with B-cell neoplasms. This regimen was also better
tolerated than similar fludarabine-based regimen. The response rates were improved with
addition of rituximab, anti CD 20 antibody, to the above regimen. Studies have demonstrated
synergy between bendamustine and purine analogs like pentostatin in killing cancer cell
types of CLL and NHL. The combination of these three drugs (pentostatin, bendamustine and
ofatumumab) has not been tested in clinical setting and we anticipate that the combination
regimen will be more active than individual drugs alone. The aim of this trial is to find a
safe dose of bendamustine to be used in combination with pentostatin and ofatumumab in
patients with previously treated CLL and B-cell NHL.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) of Bendamustine
The primary objective of this study is to determine the dose of bendamustine in combination with pentostatin and ofatumumab at which <33% of patients with relapsed Non-Hodgkin's Lymphoma (NHL) or Chronic Lymphocytic Leukemia (CLL) experience severe toxicity; and to assess the toxicity of this regimen.
Up to 6 months
Mark Weiss, MD
Thomas Jefferson University
United States: Institutional Review Board
|Thomas Jefferson University||Philadelphia, Pennsylvania 19107-6541|