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| ID | Type | Description | Link |
|---|---|---|---|
| Protocol# X05184 | Other Grant/Funding Number | Millennium |
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| Name | Class |
|---|---|
| Millennium Pharmaceuticals, Inc. | INDUSTRY |
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This is a Phase I/II trial designed to study the toxicity and Maximum Tolerated Dose (MTD) of bortezomib in combination with BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT) and to obtain a preliminary estimate of the response rate to this combination.
Primary Objective:The primary objective of the study is to evaluate the toxicity and determine the maximum tolerated dose (MTD) of bortezomib when added to a standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) conditioning regimen followed by autologous hematopoietic stem cell transplantation (ASCT).
Secondary Objective: The secondary objective of the study is to obtain a preliminary estimate of the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) with this regimen.
Enrolled subjects will receive bortezomib in combination with BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (AHSCT). Phase I treatment will administer bortezomib in four dose cohorts,in addition to the BEAM and ASCT. Three patients will be accrued in each dose cohort with enrollment starting at dose cohort. These subjects will be evaluated to establish the maximum tolerated dose of bortezomib in combination with BEAM autologous peripheral blood stem cell transplantation. Once established, the maximum tolerated dose will be utilized in treating an additional 20 subjects.
Follow-Up: Data collected will be utilized to obtain a preliminary estimate of the overall response rate, progressions free survival and overall survival using this regimen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bortezomib Dose Escalation | Experimental | The phase I section of the study will follow a standard 3 + 3 design to determine the maximum tolerated dose (MTD) of bortezomib when added to a standard BEAM (BCNU (carmustine), etoposide, cytarabine, melphalan) conditioning regimen followed by autologous hematopoietic stem cell transplantation (ASCT). After the MTD is defined, additional patients will enroll in Phase II to obtain preliminary estimates of survival using the Phase I regimen. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bortezomib | Drug | Patients will receive bortezomib in four dose cohorts ( .8. 1.0, 1.3, 1.5 mg/m²). Patients will receive bortezomib on days -11, -8, -5, and -2 before infusion of autologous stem cells. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Bortezomib | The maximum tolerated dose (MTD) is defined to be the dose cohort below which 3 of 6 patients experience dose limiting toxicity (DLT), or the highest dose cohort of 1.5 mg/m², if 2 DLT were not observed at any dose cohort. | 14 months |
| Measure | Description | Time Frame |
|---|---|---|
| Preliminary Estimate of Overall Response Rate (ORR) | To obtain a preliminary estimate of overall response rate (ORR). The overall response rate is calculated as the number of patients who achieved complete response (CR) and partial response (PR) divided by the total number of evaluable patients. | 100 day post autologous hematopoietic stem cell transplantation (ASCT), one year post ASCT |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Julie M Vose, MD | University of Nebraska | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Nebraska Medical Center | Omaha | Nebraska | 68198-7680 | United States |
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Subjects were screened and enrolled at an academic medical center in the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1: Bortezomib-0.8 mg/m² | Bortezomib dose - 0.8 mg/m² will be added to standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) regimen followed by autologous hematopoietic stem cell transplantation (ASCT). |
| FG001 | Phase 1: Bortezomib-1.0 mg/m² |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) | Drug | All study patients will receive BEAM per the standard institution protocol: BCNU (carmustine): 300 mg/m²on day -5 etoposide 100 mg/m² twice daily on days -5, -4, -3, and -2 cytarabine 100 mg/m² twice daily on days -5, -4, -3, -2 melphalan: 140 mg/m² on day -1 before infusion of autologous stem cells. |
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| Progression-free Survival (PFS), and Overall Survival (OS) | To obtain a preliminary estimate of PFS and OS. Overall survival (OS) is defined as time from the first chemotherapy administered on the transplant trial until death from any cause. Progression free survival (PFS)is defined as time from therapy until relapse, progression, or death from any cause. | one year post autologous hematopoietic stem cell transplantation (ASCT) , 5 years post ASCT |
Bortezomib dose - 1.0 mg/m² will be added to standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) regimen followed by autologous hematopoietic stem cell transplantation (ASCT). |
| FG002 | Phase 1: Bortezomib-1.3 mg/m² | Bortezomib dose - 1.3 mg/m² will be added to standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) regimen followed by autologous hematopoietic stem cell transplantation (ASCT). |
| FG003 | Phase 1: Bortezomib-1.5 mg/m² | Bortezomib dose - 1.5 mg/m² will be added to standard BEAM (carmustine (BCNU), etoposide, cytarabine, melphalan) regimen followed by autologous hematopoietic stem cell transplantation (ASCT). |
| FG004 | Phase II: Bortezomib-1.5 mg/m² | Obtain a preliminary estimate of the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) with maximum tolerated dose regimen. |
| FG005 | Phase II: Bortezomib-1.3 mg/m² | Obtain a preliminary estimate of the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) with maximum tolerated dose regimen. |
| FG006 | Phase II:Bortezomib-1.0 mg/m² | Obtain a preliminary estimate of the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) with maximum tolerated dose regimen. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase I/II | In Phase 1 of the study, bortezomib was administered in 4 dose cohorts: 0.8 mg/m², 1.0 mg/m², 1.3 mg/m² and 1.5 mg/m². Bortezomib was given on days -11, -8, -5, and -2. All study patients received BEAM conditioning: carmustine (BCNU) 300 mg/m² on day -5, etoposide 100 mg/m² twice daily on days -5, -4, -3, and -2, cytarabine 100 mg/m² twice daily on days -5, -4, -3, and -2, and melphalan 140 mg/m² on day -1 before infusion of autologous stem cells. The objective of phase 1 was to determine the maximum tolerated dose (MTD) of bortezomib in this setting. The MTD was defined by observing any nonhematologic transplantation-related toxicity higher than grade 2 on the Bearman scale occurring between day -11 and engraftment. After the MTD was defined, patients were enrolled in Phase II to obtain a preliminary estimate of overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) using this regimen. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| 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 | Maximum Tolerated Dose (MTD) of Bortezomib | The maximum tolerated dose (MTD) is defined to be the dose cohort below which 3 of 6 patients experience dose limiting toxicity (DLT), or the highest dose cohort of 1.5 mg/m², if 2 DLT were not observed at any dose cohort. | The MTD in Phase I was initially determined to be 1.5 mg/m2 but was later decreased to 1 mg/m2. | Posted | Number | mg/m² | 14 months |
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| Secondary | Preliminary Estimate of Overall Response Rate (ORR) | To obtain a preliminary estimate of overall response rate (ORR). The overall response rate is calculated as the number of patients who achieved complete response (CR) and partial response (PR) divided by the total number of evaluable patients. | One hundred days after autologous hematopoietic stem cell transplantation (ASCT), 40 participants were evaluable for response. At year one post ASCT, 38 participants were evaluable for response. Participants evaluable for the secondary endpoints (Phase II) are those who complete the transplant procedure. | Posted | Number | participants | 100 day post autologous hematopoietic stem cell transplantation (ASCT), one year post ASCT |
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| Secondary | Progression-free Survival (PFS), and Overall Survival (OS) | To obtain a preliminary estimate of PFS and OS. Overall survival (OS) is defined as time from the first chemotherapy administered on the transplant trial until death from any cause. Progression free survival (PFS)is defined as time from therapy until relapse, progression, or death from any cause. | There were 38 evaluable patients at one year post autologous hematopoietic stem cell transplantation (ASCT). | Posted | Number | 95% Confidence Interval | percentage of participants | one year post autologous hematopoietic stem cell transplantation (ASCT) , 5 years post ASCT |
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3 years
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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 | Phase I: Intervention | In Phase I of the study, bortezomib will be administered in 4 dose cohorts: .8 mg/m2 , 1.0 mg/m2, 1.3 mg/m2, and1.5 mg/m2. Three patients will be accrued in each dose cohort with enrollment starting at dose cohort 1 (.8 mg/m2). Bortezomib will be given on days -11,-8, -5, and -2. All study patients will receive BEAM conditioning per our standard institution protocol: carmustine (BCNU) 300 mg/m2 on day -5,etoposide 100 mg/m2 twice daily on days -5, -4, -3, and -2, cyatabine100 mg/m2 twice daily on days -5, -4, -3, and -2, and melphalan 140 mg/m2 on day -1 before infusion of autologous stem cells. The objective of phase I is to determine the maximum tolerated dose (MTD) of bortezomib in this setting. After the MTD is defined, another 20 patients will be enrolled in the Phase II portion of this protocol to obtain a preliminary estimate of the response rate. | 0 | 13 | 13 | 13 | ||
| EG001 | Phase II: Survival | Patients enrolled to obtain a preliminary estimate of ORR, Progression-free survival, and overall survival (OS) using this regimen. | 1 | 29 | 29 | 29 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| adynamic ileus | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenic Fever | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Peripheral Neuropathy | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Vasovagal syncope/orthostatic hypotension | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Ileus | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Julie M Vose | University of Nebraska Medical Center | 402-559-3848 | jmvose@unmc.edu |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D020522 | Lymphoma, Mantle-Cell |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000069286 | Bortezomib |
| D002330 | Carmustine |
| D005047 | Etoposide |
| D003561 | Cytarabine |
| D008558 | Melphalan |
| ID | Term |
|---|---|
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009603 | Nitroso Compounds |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Unknown or Not Reported |
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