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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2018-01830 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2006-0066 | Other Identifier | M D Anderson Cancer Center | |
| P30CA016672 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This phase II trial studies the side effects and best dose of bortezomib when given with chemotherapy and to see how well they work in treating participants with lymphoid malignancies undergoing stem cell transplant. Giving chemotherapy before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the participant they may help the participant's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells called graft versus host disease. Giving tacrolimus and methotrexate after the transplant may stop this from happening. Giving bortezomib and chemotherapy may work better in treating participants with lymphoid malignancies undergoing a stem cell transplant.
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of Velcade (bortezomib) in patients with lymphoid malignancies undergoing allogeneic peripheral blood stem cell or bone marrow transplantation.
II. To determine the 1-year disease-free-survival (DFS) and the toxicity profile of Velcade (bortezomib) in patients with lymphoid malignancies undergoing allogeneic peripheral blood stem cell or bone marrow transplantation.
SECONDARY OBJECTIVES:
I. To compare the incidence of graft versus host disease (GVHD) with historical controls.
OUTLINE: This is a dose-escalation study of bortezomib.
Participants receive carmustine intravenously (IV) over 1 hour on day -6, cytarabine IV over 1 hour twice daily (BID) on days -5 to -2, etoposide IV over 3 hours BID on days -5 to -2, and melphalan IV over 30 minutes on day -1. Participants also receive rituximab IV on days -13, -6, +1, and +8, and bortezomib IV over 1 minute on days -13, -6, -1, and +2. Participants receiving a matched unrelated or mismatched donor transplant also receive anti-thymocyte globulin IV over 4-6 hours on days -6 and -5. Participants then undergo allogeneic hematopoietic stem cell transplantation over 30-45 minutes on day 0 and receive filgrastim subcutaneously (SC) once daily (QD) starting on day +7 until blood counts return to normal level. Participants receive tacrolimus IV starting on day -2 changing to orally (PO) before leaving the hospital for 6-8 months after the transplant. Participants also receive methotrexate IV over a few minutes on days +1, +3, and +6 and those receiving a matched unrelated or mismatched donor transplant also receive methotrexate IV on day +11.
After completion of study treatment, participants are followed up at 1 month, every 3 months for 1 year, and then every 6 months for 5 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (chemotherapy, transplant, filgrastim, tacrolimus) | Experimental | See Detailed Description |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplantation | Procedure | Undergo allogeneic hematopoietic stem cell transplantation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicity (DLT) | To determine the maximum tolerated dose(MTD) of velcade and dose limiting toxicity(DLT). A dose limiting toxicity (DLT) was defined as a grade 3-4 neurological toxicity, graft failure, or death due to GvHD. The Commom Terminlogy Criteria for Adverse Events v3.0 was used. | From start of treatment to 90 days after the start of treatment |
| Disease-free Survival | To determine DFS at 1 year post transplant. | At 1 year |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Issa Khouri | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| M D Anderson Cancer Center | Houston | Texas | 77030 | United States |
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| Label | URL |
|---|---|
| MD Anderson Cancer Center Website | View source |
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Patients enrolled at MD Anderson clinic from February 2007 through May 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | Velcade Dose Level 1 | BEAM (Carmustine/Etoposide/Cytarabine/Melphalan) + Rituxan + ATG (Thymoglobulin) (MUD pts only) + Velcade 1.0mg/m2 + ALLO SCT |
| FG001 | Velcade Dose Level 2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 4, 2017 |
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|
| Anti-Thymocyte Globulin | Biological | Given IV |
|
|
| Bortezomib | Drug | Given IV |
|
|
| Carmustine | Drug | Given IV |
|
|
| Cytarabine | Drug | Given IV |
|
|
| Etoposide | Drug | Given IV |
|
|
| Filgrastim | Biological | Given SC |
|
|
| Melphalan | Drug | Given IV |
|
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| Methotrexate | Drug | Given IV |
|
|
| Rituximab | Biological | Given IV |
|
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| Tacrolimus | Drug | Given IV and PO |
|
|
BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.3mg/m2 + ALLO SCT
| FG002 | Velcade Dose Level 3 | BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.6mg/m2 + ALLO SCT |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Patients up to 70 years of age with any histological subtype of CD20+ lymphoid malignancy or T-Cell lymphoid malignancy who were not eligible for a non-myeloablative transplant.
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| ID | Title | Description |
|---|---|---|
| BG000 | Velcade Dose Level 1 | BEAM + Rituxan + ATG(MUD pts only) + Velcade (1-1.3mg/m2) + ALLO SCT |
| BG001 | Velcade Dose Level 2 | BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.3mg/m2 + ALLO SCT |
| BG002 | Velcade Dose Level 3 | BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.6mg/m2 + ALLO SCT |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Breakdown of Disease by Number of Participants in each Dose Level | Patients up to 70 years of age with any histological subtype of CD20+ lymphoid malignancy or T-Cell lymphoid malignancy who were not eligible for a non-myeloablative transplant. | Count of Participants | Participants |
|
| 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 | Number of Participants With Dose Limiting Toxicity (DLT) | To determine the maximum tolerated dose(MTD) of velcade and dose limiting toxicity(DLT). A dose limiting toxicity (DLT) was defined as a grade 3-4 neurological toxicity, graft failure, or death due to GvHD. The Commom Terminlogy Criteria for Adverse Events v3.0 was used. | Patients up to 70 years of age with any histological subtype of CD20+ lymphoid malignancy or T-Cell lymphoid malignancy who were not eligible for a non-myeloablative transplant. | Posted | Count of Participants | Participants | From start of treatment to 90 days after the start of treatment |
|
|
| ||||||||||||||||||||||||||||||||
| Primary | Disease-free Survival | To determine DFS at 1 year post transplant. | Patients up to 70 years of age with any histological subtype of CD20+ lymphoid malignancy or T-Cell lymphoid malignancy who were not eligible for a non-myeloablative transplant. | Posted | Count of Participants | Participants | At 1 year |
|
|
Up to 100 Days post transplant
There were no participants enrolled on Velcade dose level 3
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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 | Velcade Dose Level 1 | BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.0mg/m2 + ALLO SCT | 6 | 36 | 6 | 36 | 36 | 36 |
| EG001 | Velcade Dose Level 2 | BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.3mg/m2 + ALLO SCT | 2 | 3 | 2 | 3 | 3 | 3 |
| EG002 | Gemcitabine Dose Level 3 | BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.6mg/m2 + ALLO SCT | 0 | 0 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | CTCAE v3.0 | Systematic Assessment |
| |
| Acute GvHD(graft vs Host Disease) | General disorders | CTCAE v3.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysrhythmia | Cardiac disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Decreased Cardiac Function | Cardiac disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Hypertension | Cardiac disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Fluid Overload | General disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Fever | General disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE v3.0 | Systematic Assessment |
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| Mucositis | Gastrointestinal disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Elevated Creatinine | Renal and urinary disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Hemorrhagic Cystitis | Renal and urinary disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Transaminitis | Hepatobiliary disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Infection | Infections and infestations | CTCAE v3.0 | Systematic Assessment |
| |
| Neutropenic Fever | Infections and infestations | CTCAE v3.0 | Systematic Assessment |
| |
| SOB (Shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Acute GvHD | General disorders | CTCAE v3.0 | Systematic Assessment |
| |
| Chronic GvHD | General disorders | CTCAE v3.0 | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Khouri,Issa,M.D. / Stem Cell Transplantation | UT MD Anderson Cancer Center | 713-792-8750 | ikhouri@mdanderson.org |
| Jul 24, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000961 | Antilymphocyte Serum |
| C512542 | thymoglobulin |
| D000069286 | Bortezomib |
| D002330 | Carmustine |
| C574855 | carmustine, poliferprosan 20 drug combination |
| D003561 | Cytarabine |
| D005047 | Etoposide |
| D000069585 | Filgrastim |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D008558 | Melphalan |
| D008727 | Methotrexate |
| C015342 | merphos |
| D000069283 | Rituximab |
| C000626854 | CT-P10 |
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| 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 |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| 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 |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D018942 | Macrolides |
| D007783 | Lactones |
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| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| CLL |
|
| Folicular Lymphoma |
|
| Mantle Cell Lymphoma |
|
| Marginal Zone Lymphoma |
|
| T-Cell Lymphoma |
|
|