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| ID | Type | Description | Link |
|---|---|---|---|
| URCC-U9404 | |||
| URCC-RSRB-10368 | |||
| MILLENNIUM-VEL-03-079 | |||
| LILLY-B9E-US-X433 | |||
| DFCI-04388 |
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RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with gemcitabine hydrochloride may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with gemcitabine hydrochloride works in treating patients with relapsed or refractory Hodgkin's lymphoma.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, pilot study.
Patients receive bortezomib IV on days 1, 4, 8, and 11 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 2 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bortezomib, Gemcitabine Hdrochloride | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| bortezomib | Drug |
| ||
| gemcitabine hydrochloride |
| Measure | Description | Time Frame |
|---|---|---|
| Response Rate After 2 Courses of Therapy | Response was evaluated after two cycles of therapy using the 1999 Cheson response criteria. All responses were based on CT scans. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. For patients who had FDG-PET imaging, metabolic response was defined as a decrease in the standardized uptake value in target lesions (regions of abnormal FDG uptake on pretreatment FDG-PET images) to below three on posttreatment FDG-PET imaging). All PET scans were reviewed and interpreted by a single radiologist (SV). | 21 Days/course for up to 2 courses |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Proteasome Activity Compared to Baseline (Cycle 1) | Peripheral blood (40 ml) was collected on cycle 1, day 1 of prebortezomib at baseline and 2 hrs post-bortezomib treatment. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 microliters was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and 2 hrs (day1, cycle 1) was calculated. |
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DISEASE CHARACTERISTICS:
Histologically confirmed Hodgkin's lymphoma
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 1 cm by physical exam or imaging studies
No history of non-Hodgkin's lymphoma
No history of other hematological malignancy
PATIENT CHARACTERISTICS:
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
Pulmonary
Immunologic
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Other
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| Name | Affiliation | Role |
|---|---|---|
| Jonathan W. Friedberg, MD | James P. Wilmot Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston | Massachusetts | 02115 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18504251 | Result | Mendler JH, Kelly J, Voci S, Marquis D, Rich L, Rossi RM, Bernstein SH, Jordan CT, Liesveld J, Fisher RI, Friedberg JW. Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma. Ann Oncol. 2008 Oct;19(10):1759-64. doi: 10.1093/annonc/mdn365. Epub 2008 May 25. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Bortezomib, Gemcitabine Hydrochloride | bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Bortezomib, Gemcitabine Hydrochloride | bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Response Rate After 2 Courses of Therapy | Response was evaluated after two cycles of therapy using the 1999 Cheson response criteria. All responses were based on CT scans. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. For patients who had FDG-PET imaging, metabolic response was defined as a decrease in the standardized uptake value in target lesions (regions of abnormal FDG uptake on pretreatment FDG-PET images) to below three on posttreatment FDG-PET imaging). All PET scans were reviewed and interpreted by a single radiologist (SV). | Posted | Number | participants | 21 Days/course for up to 2 courses |
|
days 1 and 8 of each cycle of therapy, up to 2 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bortezomib, Gemcitabine Hydrochloride | bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
Trial was stopped early by the Data Safety Monitoring Committee due to unexpected toxicity with no improvement in the response rate compared with gemcitabine alone. Trial was prespecified to be stopped early if these criteria were met.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jonathan W. Friedberg | University of Rochester | 585-273-4150 | jonathan_friedberg@urmc.rochester.edu |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D006689 | Hodgkin Disease |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000069286 | Bortezomib |
| D000093542 | Gemcitabine |
| ID | Term |
|---|---|
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
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| Drug |
|
| baseline to 2 hours |
| Change in Proteasome Activity Compared to Baseline (Cycle 2) | Peripheral blood (40 ml) was collected at baseline and 1-2 weeks after cycle 2, day 11 post-bortezomib treatment. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 microliters was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and 2 hrs (day1, cycle 1) was calculated. | baseline and 1-2 weeks after cycle 2, day 11 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center |
| Rochester |
| New York |
| 14642 |
| United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule. |
|
|
| Secondary | Change in Proteasome Activity Compared to Baseline (Cycle 1) | Peripheral blood (40 ml) was collected on cycle 1, day 1 of prebortezomib at baseline and 2 hrs post-bortezomib treatment. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 microliters was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and 2 hrs (day1, cycle 1) was calculated. | Samples were not collected on one patient, so only 17 patients were analyzed. | Posted | Median | Full Range | Percentage of change in proteosome activ | baseline to 2 hours |
|
|
|
| Secondary | Change in Proteasome Activity Compared to Baseline (Cycle 2) | Peripheral blood (40 ml) was collected at baseline and 1-2 weeks after cycle 2, day 11 post-bortezomib treatment. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 microliters was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and 2 hrs (day1, cycle 1) was calculated. | Samples were not collected on one patient, so only 17 patients were analyzed. | Posted | Median | Full Range | percentage of change in proteosome activ | baseline and 1-2 weeks after cycle 2, day 11 |
|
|
|
| 5 |
| 18 |
| 18 |
| 18 |
| leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| thrombocytompenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| elevated transaminases | Hepatobiliary disorders | Systematic Assessment |
|
| hyperglycemia | Vascular disorders | Systematic Assessment |
|
| abdominal pain/cramps | General disorders | Systematic Assessment |
|
| lymphopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| headache/migraine | Nervous system disorders | Systematic Assessment |
|
| sepsis | Infections and infestations | Systematic Assessment |
|
| DVT near line | Vascular disorders | Systematic Assessment |
|
| worsening leg ulcer | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| elevated transaminases | Hepatobiliary disorders | Systematic Assessment |
|
| hyperglycemia | Endocrine disorders | Systematic Assessment |
|
| abdominal pain/cramps | Gastrointestinal disorders | Systematic Assessment |
|
| anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| pain | General disorders | Systematic Assessment |
|
| hypocalcemia | Blood and lymphatic system disorders | Systematic Assessment |
|
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| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D001896 |
| Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |