PS-341 Alone and PS-341 Plus EPOCH Chemotherapy to Treat Non-Hodgkin's Lymphoma
Status:
Completed
Trial end date:
2009-07-01
Target enrollment:
Participant gender:
Summary
This study will examine the safety and effectiveness of an experimental drug called
Bortezomib (PS-341), given alone and in combination with a chemotherapy regimen called
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin and Filgrastim (EPOCH), in
treating non-Hodgkin's B-cell lymphoma. In the laboratory, PS-341 kills lymphoma cells and
makes them more sensitive to chemotherapy. The EPOCH treatment regimen includes the drugs
doxorubicin, etoposide, vincristine, cyclophosphamide, prednisone, and filgrastim.
Patients 18 years of age and older with an aggressive non-Hodgkin's lymphoma that has
relapsed after treatment or is not responding to chemotherapy may be eligible for this study.
Candidates will be screened with a medical history and physical examination. Other tests that
may be required include blood and urine tests; lung function studies; imaging tests such as
magnetic resonance imaging, computed tomography and x-rays; and biopsy (surgical removal of a
small tissue sample) of tumor, bone marrow, or other tissue.
Upon entering the study, all participants will receive PS-341. The drug is given as a 3- to
5-second intravenous (through a vein) injection twice a week for 2 weeks. This is followed by
a 1-week rest. Each 3-week period comprises one treatment cycle. The number of cycles a
patient receives depends on how well he or she responds to the drug. Patients who do not have
a complete remission or whose tumor grows on this therapy will be offered PS-341 in
combination with up to six cycles of EPOCH chemotherapy. The treatment for patients taking
PS-341 plus EPOCH is as follows:
- PS-341, given by 3- to 5-second intravenous (IV) injection on days 1 and 4 of each
cycle.
- Doxorubicin, etoposide, and vincristine, given by continuous IV infusion over 4 days,
beginning on day 1 and ending on day 5 of each cycle. The drugs are delivered through a
lightweight portable infusion pump to an indwelling IV catheter (plastic tube) in a
vein.
- Cyclophosphamide, given by IV infusion over 15 minutes on day 5 of each cycle.
- Prednisone, given by mouth (pills) twice a day on days 1 through 5 of each cycle.
- Filgrastim, given by injection under the skin starting on day 6 of each cycle and
continuing until the white blood cell count increases or until day 19 of the cycle.
Patients also take a combination of antibiotics 3 days a week during EPOCH to prevent
infection while resistance is lowered because of the chemotherapy. Etoposide, doxorubicin,
and cyclophosphamide doses are adjusted as needed, based on white blood cell counts of the
previous cycle. The first patients in the study will receive a low dose of PS-341. The dose
will be increased in subsequent small groups of patients as long as the preceding dose is
well tolerated.
Drug therapy for patients who are candidates for bone marrow transplant will be tailored to
permit transplantation. Patients who are not eligible for or who choose not to have a bone
marrow transplant will be followed at the National Institutes of Health (NIH) every 3 months
the first year, every 4 months the second year, every 6 months the third year, and then once
a year until their disease progresses or the study ends. Patients may have tumor and bone
marrow biopsies, blood draws, and computed tomography (CT) scans periodically to evaluate
disease status and drug side effects.