Ignite Creation Date:
2024-05-05 @ 11:30 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00054665
Status:
COMPLETED
Last Update Posted:
2012-09-11
First Post:
2003-02-05
Brief Title:
PS-341 Alone and PS-341 Plus EPOCH Chemotherapy to Treat Non-Hodgkins Lymphoma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
PS-341 and PS-341 Epoch Chemotherapy and Molecular Profiling in Relapsed or Refractory Diffuse Large B-Cell Lymphomas
Status:
COMPLETED
Status Verified Date:
2012-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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-Hodgkins 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-Hodgkins 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
Patients 18 years of age and older with an aggressive non-Hodgkins 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
Detailed Description:
Diffuse large B-cell lymphomas DLBCL have been molecularly sub-classified into germinal center like B-cell GCB and activated B-cell like ABC DLBCL Clinically the ABC subtype has a significantly higher rate of drug resistance and lower survival The ABC subtype has overexpression of nuclear factor-kappa B NF-kB with transcriptional activation of B cell lymphoma 2 bcl-2 which may account for the drug resistance The ability of NF-kB to inhibit responses to cancer therapeutic agents may also contribute to the refractory clinical behavior of ABC subtype and inhibition of NF-kB can synergize with the chemotherapy to kill tumor cells This protocol aims to study the affect of NF-kB inhibition through proteasome inhibition by PS-341 on response to PS-341 and PS-341 with EPOCH chemotherapy in DLBCL It will also assess the affect of PS-341 on NF-kB and BCL-2 tumor expression by microarray and provide information on the specificity of PS-341
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-C-0096 | None | None | None |