PS-341 Alone and PS-341 Plus EPOCH Chemotherapy to Treat Non-Hodgkin's Lymphoma
PS-341 and PS-341 + Epoch Chemotherapy and Molecular Profiling in Relapsed or Refractory Diffuse Large B-Cell Lymphomas
2 other identifiers
interventional
50
1 country
2
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-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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2003
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2003
CompletedFirst Submitted
Initial submission to the registry
February 5, 2003
CompletedFirst Posted
Study publicly available on registry
February 6, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2009
CompletedResults Posted
Study results publicly available
September 11, 2012
CompletedSeptember 11, 2012
August 1, 2012
5.6 years
February 5, 2003
June 25, 2012
August 10, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Clinical Response Rate
Clinical Response Rate is the number of participants with a partial and complete response assessed by the criteria for lymphoma. A complete response is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy and normalization of those biochemical abnormalities. Partial response is a greater than or equal to 50% decrease in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease
18 weeks
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
43 months
Study Arms (2)
Part A: PS-341 Alone
EXPERIMENTAL1.3 mg/m\^2 intravenous injection days 1, 4, 8, 11 every 3 weeks
Part B: PS-341 & EPOCH
EXPERIMENTALPS-341: level 1: 0.5 mg/m\^2 intravenous (IV) days 1, 4; level 2: 1.0 mg/m\^2 IV days 1, 4; level 3: 1.5 mg/m\^2 IV days 1, 4; level 4: 1.7 mg/m\^2 IV days 1, 4. EPOCH: Etoposide: 50 mg/m\^2 day continuous intravenous infusion (CIV) days 1-4, 96 hour infusion; Doxorubicin: 10 mg/m\^2 day CIV days 1-4, 96 hour infusion; Vincristine: 0.4 mg/m\^2 day CIV days 1-4, 96 hour infusion; Cyclophosphamide: 750 mg/m\^2 day IV day 5 bolus; Prednisone: 60 mg/m\^2 by mouth twice a day days 1-5; Filgrastim: 300 micrograms subcutaneously days 6 to absolute neutrophil count recovery greater than or equal to 5000/mm\^3. Repeat cycles every 21 days.
Interventions
1.3 mg/m\^2 intravenous injection days 1, 4, 8, 11 every 3 weeks
50 mg/m\^2 day continuous intravenous infusion (CIV) days 1-4, 96 hour infusion. Repeat cycle every 21 days.
10 mg/m\^2 day CIV days 1-4, 96 hour infusion. Repeat cycle every 21 days.
0.4 mg/m\^2 day CIV days 1-4, 96 hour infusion. Repeat cycle every 21 days.
750 mg/m\^2 day IV day 5 bolus. Repeat cycle every 21 days.
60 mg/m\^2 by mouth twice a day days 1-5. Repeat cycle every 21 days.
300 micrograms subcutaneously days 6 to absolute neutrophil count recovery greater than or equal to 5000/mm\^3. Repeat cycle every 21 days.
Eligibility Criteria
Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.
Sponsors & Collaborators
Study Sites (2)
National Cancer Institute (NCI)
Bethesda, Maryland, 20892, United States
Roswell Parck Cancer Institute
Buffalo, New York, 14263, United States
Related Publications (2)
Baldwin AS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649-83. doi: 10.1146/annurev.immunol.14.1.649.
PMID: 8717528BACKGROUNDDunleavy K, Pittaluga S, Czuczman MS, Dave SS, Wright G, Grant N, Shovlin M, Jaffe ES, Janik JE, Staudt LM, Wilson WH. Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood. 2009 Jun 11;113(24):6069-76. doi: 10.1182/blood-2009-01-199679. Epub 2009 Apr 20.
PMID: 19380866BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Wyndham Wilson, M.D.
- Organization
- National Cancer Institute, National Institues of Health
Study Officials
- PRINCIPAL INVESTIGATOR
Wyndham Wilson, M.D.
National Cancer Institute, National Institutes of Health
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Dr. Wyndham Wilson
Study Record Dates
First Submitted
February 5, 2003
First Posted
February 6, 2003
Study Start
February 1, 2003
Primary Completion
September 1, 2008
Study Completion
July 1, 2009
Last Updated
September 11, 2012
Results First Posted
September 11, 2012
Record last verified: 2012-08