Ignite Creation Date:
2024-05-05 @ 11:44 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00114738
Status:
COMPLETED
Last Update Posted:
2022-10-10
First Post:
2005-06-17
Brief Title:
EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Randomized Phase II Study of Dose-Adjusted EPOCH-Rituximab-Bortezomib EPOCH-R-B Induction Followed by Bortezomib Maintenance Versus Observation in Untreated Mantle Cell Lymphoma With Microarray Profiling and Proteomics
Status:
COMPLETED
Status Verified Date:
2022-09
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 evaluate the effectiveness of etoposide prednisone vincristine cyclophosphamide doxorubicin-rituximab EPOCH-R chemotherapy plus bortezomib for treating mantle cell lymphoma a cancer of white blood cells called lymphocytes EPOCH-R consists of the drugs prednisone etoposide doxorubicin and vincristine with the addition of a new drug called rituximab In a recent study of patients with newly diagnosed mantle cell lymphoma 92 percent had a complete remission of their disease after treatment with EPOCH-R This study will test whether adding bortezomib as maintenance therapy once chemotherapy is finished will lengthen the time before the disease relapses and improve the overall cure rate
Patients 18 years of age and older with mantle cell lymphoma may be eligible for this study Candidates are screened with a medical history and physical examination blood and urine tests electrocardiogram multi-gated acquisition scan MUGA or echocardiogram imaging studies and biopsy to determine the extent of disease and possible colonoscopy
Participants undergo treatment in three parts as follows
Part 1 Bortezomib alone Patients receive 4 doses of bortezomib over 3 weeks The drug is injected into a vein over about 30 seconds
Part 2 EPOCH-R chemotherapy plus bortezomib This phase of treatment begins 3 to 4 weeks after completing Part 1 Treatment is given on an outpatient basis in six 3-week cycles with all drugs administered over the first 5 days of each cycle Patients take prednisone by mouth on days 1 to 5 and etoposide doxorubicin and vincristine as a 96-hour infusion through a vein over days 1 to 5 The infused drugs are delivered through a lightweight portable infusion pump Rituximab is given by vein over several hours on day 1 immediately before the chemotherapy infusion begins Bortezomib is given by vein over 30 seconds on day 1 before the rituximab and again on day 4 Cyclophosphamide is given by vein over about 15 minutes on day 5 immediately after the chemotherapy infusion is completed Patients are taught how to self inject granulocyte colony stimulating factor G-CSF a drug that helps boost white cell counts after chemotherapy They inject the drug under the skin like an insulin shot for 10 days of each cycle beginning day 6 Patients also take an antibiotic to help prevent infection during chemotherapy
Part 3 Bortezomib alone After completing EPOCH-R-B therapy patients are randomly assigned to receive or not to receive bortezomib alone The drug is given in 2 doses over 5 days with a break of 16 days before the next dose These 3-week cycles continue for up to 18 months or until the disease comes back or worsens Patients who are assigned to the group that does not receive bortezomib will be offered the drug if their disease relapses
During therapy patients have tests performed on their bone marrow tumor tissue blood or other fluids to look at different genes and proteins that may be involved in the development of their lymphoma or the reaction of the immune system A tissue biopsy is done before treatment begins and a day after treatment starts Disease progress is followed with computed tomography CT scans and blood tests When treatment is completed patients whose cancer has disappeared are scheduled for periodic follow-up examinations and tests Those whose disease remains or recurs may be offered participation in another protocol if an appropriate one is available or are returned to the care of their local physician
Patients 18 years of age and older with mantle cell lymphoma may be eligible for this study Candidates are screened with a medical history and physical examination blood and urine tests electrocardiogram multi-gated acquisition scan MUGA or echocardiogram imaging studies and biopsy to determine the extent of disease and possible colonoscopy
Participants undergo treatment in three parts as follows
Part 1 Bortezomib alone Patients receive 4 doses of bortezomib over 3 weeks The drug is injected into a vein over about 30 seconds
Part 2 EPOCH-R chemotherapy plus bortezomib This phase of treatment begins 3 to 4 weeks after completing Part 1 Treatment is given on an outpatient basis in six 3-week cycles with all drugs administered over the first 5 days of each cycle Patients take prednisone by mouth on days 1 to 5 and etoposide doxorubicin and vincristine as a 96-hour infusion through a vein over days 1 to 5 The infused drugs are delivered through a lightweight portable infusion pump Rituximab is given by vein over several hours on day 1 immediately before the chemotherapy infusion begins Bortezomib is given by vein over 30 seconds on day 1 before the rituximab and again on day 4 Cyclophosphamide is given by vein over about 15 minutes on day 5 immediately after the chemotherapy infusion is completed Patients are taught how to self inject granulocyte colony stimulating factor G-CSF a drug that helps boost white cell counts after chemotherapy They inject the drug under the skin like an insulin shot for 10 days of each cycle beginning day 6 Patients also take an antibiotic to help prevent infection during chemotherapy
Part 3 Bortezomib alone After completing EPOCH-R-B therapy patients are randomly assigned to receive or not to receive bortezomib alone The drug is given in 2 doses over 5 days with a break of 16 days before the next dose These 3-week cycles continue for up to 18 months or until the disease comes back or worsens Patients who are assigned to the group that does not receive bortezomib will be offered the drug if their disease relapses
During therapy patients have tests performed on their bone marrow tumor tissue blood or other fluids to look at different genes and proteins that may be involved in the development of their lymphoma or the reaction of the immune system A tissue biopsy is done before treatment begins and a day after treatment starts Disease progress is followed with computed tomography CT scans and blood tests When treatment is completed patients whose cancer has disappeared are scheduled for periodic follow-up examinations and tests Those whose disease remains or recurs may be offered participation in another protocol if an appropriate one is available or are returned to the care of their local physician
Detailed Description:
Background
Mantle cell lymphoma MCL presents a clinical challenge because it is aggressive and incurable with chemotherapy Therefore novel treatment approaches are needed
MCL has overexpression of NF-kappa B NF-kappa B a transcription factor that affects cell growth and survival and cyclin D1 that affects cell cycle and growth These proteins appear to be involved in the pathogenesis of MCL
Bortezomib a proteasome inhibitor that inhibits NF-kappa B and cyclin D1 has demonstrated activity in patients with relapsed or refractory MCL
Dose-adjusted-etoposide prednisone vincristine cyclophosphamide doxorubicin-rituximab EPOCH-R has excellent activity in MCL with a complete response CR rate of 92 but patients eventually relapse
Objective
Determine the progression free survival PFS and overall survival OS of dose-adjusted etoposide doxorubicin and cyclophosphamide with vincristine prednisone and rituximabbortezomib DA-EPOCH-RB followed by bortezomib maintenance versus observation
Eligibility
Diagnosis of mantle cell lymphoma
No prior treatment except for local radiation or a short course of steroids for control of symptoms
Age greater than or equal to 18 years old
Adequate major organ function unless impairment is due to lymphoma
Study Design
To assess the clinical activity and biological effects of bortezomib patients will initially receive one cycle of bortezomib alone with sequential tumor biopsies for microarray analysis
All patients will then receive Dose-adjusted DA-EPOCH-RB for 6 cycles and if they have at least a PR this will be followed by randomization to either immediate bortezomib maintenance x 18 months or to observation followed by bortezomib if progression occurs This study has as a primary goal to describe progression free survival PFS and overall survival of early bortezomib maintenance versus observation following induction with bortezomib followed by DA-EPOCH-RB Important secondary goals are to assess response and toxicity to bortezomib alone or DA-EPOCH-RB to evaluate time to progression after receiving bortezomib following progression on an observation arm and to assess the biological effects of bortezomib on untreated MCL
Mantle cell lymphoma MCL presents a clinical challenge because it is aggressive and incurable with chemotherapy Therefore novel treatment approaches are needed
MCL has overexpression of NF-kappa B NF-kappa B a transcription factor that affects cell growth and survival and cyclin D1 that affects cell cycle and growth These proteins appear to be involved in the pathogenesis of MCL
Bortezomib a proteasome inhibitor that inhibits NF-kappa B and cyclin D1 has demonstrated activity in patients with relapsed or refractory MCL
Dose-adjusted-etoposide prednisone vincristine cyclophosphamide doxorubicin-rituximab EPOCH-R has excellent activity in MCL with a complete response CR rate of 92 but patients eventually relapse
Objective
Determine the progression free survival PFS and overall survival OS of dose-adjusted etoposide doxorubicin and cyclophosphamide with vincristine prednisone and rituximabbortezomib DA-EPOCH-RB followed by bortezomib maintenance versus observation
Eligibility
Diagnosis of mantle cell lymphoma
No prior treatment except for local radiation or a short course of steroids for control of symptoms
Age greater than or equal to 18 years old
Adequate major organ function unless impairment is due to lymphoma
Study Design
To assess the clinical activity and biological effects of bortezomib patients will initially receive one cycle of bortezomib alone with sequential tumor biopsies for microarray analysis
All patients will then receive Dose-adjusted DA-EPOCH-RB for 6 cycles and if they have at least a PR this will be followed by randomization to either immediate bortezomib maintenance x 18 months or to observation followed by bortezomib if progression occurs This study has as a primary goal to describe progression free survival PFS and overall survival of early bortezomib maintenance versus observation following induction with bortezomib followed by DA-EPOCH-RB Important secondary goals are to assess response and toxicity to bortezomib alone or DA-EPOCH-RB to evaluate time to progression after receiving bortezomib following progression on an observation arm and to assess the biological effects of bortezomib on untreated MCL
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-C-0170 | None | None | None |