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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-104 | Other Identifier | CCRRC | |
| JT 3048 | Other Identifier | JeffTrial Number |
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Trial was closed due to poor accrual.
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This phase II trial studies how well haploidentical donor hematopoietic stem cell transplant works in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Giving an infusion of the donor's T cells (donor lymphocyte infusion) may replace the patient's immune cells and help destroy any remaining cancer cells. When the stem cells from a related donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
PRIMARY OBJECTIVES:
I. Examine the 1 year disease free survival (DFS) rate of patients with maternal donors or sibling donors who share the maternal haplotype (maternal group) and compare them to patients receiving cells from donors who have points from other characteristics such as killer immunoglobulin-like receptor (KIR) ligand mismatching, minor histocompatibility antigen (MHag) differences, or number of human leukocyte antigen (HLA) mismatches (non-maternal group).
SECONDARY OBJECTIVES:
I. Assess the incidences of relapse and graft-versus-host disease (GVHD) in maternal recipients whose only eligible donors are offspring.
II. Assess the incidence of grades III-IV GVHD in female recipients with male donors.
III. Compare the rates of DFS in recipient-donor combinations in which there is at least 1 KIR ligand mismatch versus those without a KIR ligand mismatch.
OUTLINE:
Patients undergo total body irradiation (TBI) twice daily (BID) on days -9 to -6, undergo donor lymphocyte infusion (DLI) on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -3 and -2.
TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.
After completion of study treatment, patients are followed up at 90, 180, and 270 days, and 1 year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (haploidentical allogeneic HSCT) | Experimental | Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Total-body irradiation | Radiation | Undergo TBI |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Disease-free Survival (DFS) | Disease free survival (DFS), defined as the time to death, relapse or disease progression. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Relapse of Disease | Relapse of Disease is defined as the return of a disease or the signs and symptoms of a disease after a period of improvement. Relapse is almost always associated with the immunological failure of the donor immune system to recognize and/or respond to reemergence of a tumor. The number of participants with relapse of disease will be collected. | Up to 1 year |
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Inclusion Criteria:
Any patient with a hematologic or oncologic diagnosis without morphological evidence of disease in which allogeneic HSCT is thought to be beneficial.
Patients must have a related donor who is a two or more allele mismatch at the HLA-A; B; C; DR loci.
Patients must have adequate organ function:
Performance status > 80% (TJU Karnofsky)
Hematopoietic Comorbidity Index (HCT-CI) Score < 5 Points
Patients must be willing to use contraception if they have childbearing potential
Able to give informed consent, or if decisionally impaired, have a legal next of kin or guardian that can give informed consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dolores Grosso, DNP, CRNP | Thomas Jefferson University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
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| Label | URL |
|---|---|
| Thomas Jefferson University Hospitals | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Haploidentical Allogeneic HSCT) | Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28. Total-body irradiation: Undergo TBI Donor lymphocytes infusion (DLI): Undergo DLI Cyclophosphamide: Given IV Allogeneic hematopoietic stem cell transplantation (HSCT): Undergo haploidentical allogeneic HSCT Tacrolimus: Given IV Mycophenolate mofetil: Given IV |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Donor lymphocytes infusion (DLI) | Biological | Undergo DLI |
|
|
| Cyclophosphamide | Drug | Given IV |
|
|
| Allogeneic hematopoietic stem cell transplantation (HSCT) | Procedure | Undergo haploidentical allogeneic HSCT |
|
| Tacrolimus | Drug | Given IV |
|
|
| Mycophenolate mofetil | Drug | Given IV |
|
|
| Rate of Grade III-IV GVHD in Female Recipients With Male Donors | The rates of grade III-IV GVHD in female recipients with male donors will be computed with corresponding exact binomial 95% confidence intervals. | Up to 1 year |
| The Rates of Grade III-IV GVHD in Female Recipients With Male Donors Will be Computed With Corresponding Exact Binomial 95% Confidence Intervals. | The difference in DFS in recipient-donor combinations in which there is at least 1 KIR ligand mismatch versus those without a KIR ligand mismatch will be tested using log-rank test. | Up to 1 year |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Haploidentical Allogeneic HSCT) | Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28. Total-body irradiation: Undergo TBI Donor lymphocytes infusion (DLI): Undergo DLI Cyclophosphamide: Given IV Allogeneic hematopoietic stem cell transplantation (HSCT): Undergo haploidentical allogeneic HSCT Tacrolimus: Given IV Mycophenolate mofetil: Given IV |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | 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 |
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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 | Number of Participants With Disease-free Survival (DFS) | Disease free survival (DFS), defined as the time to death, relapse or disease progression. | Posted | Count of Participants | Participants | 1 year |
|
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| |||||||||||||||||||||||||||
| Secondary | Number of Participants With Relapse of Disease | Relapse of Disease is defined as the return of a disease or the signs and symptoms of a disease after a period of improvement. Relapse is almost always associated with the immunological failure of the donor immune system to recognize and/or respond to reemergence of a tumor. The number of participants with relapse of disease will be collected. | Posted | Count of Participants | Participants | Up to 1 year |
|
| ||||||||||||||||||||||||||||
| Secondary | Rate of Grade III-IV GVHD in Female Recipients With Male Donors | The rates of grade III-IV GVHD in female recipients with male donors will be computed with corresponding exact binomial 95% confidence intervals. | No data were collected or analyzed. | Posted | Up to 1 year |
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| |||||||||||||||||||||||||||||
| Secondary | The Rates of Grade III-IV GVHD in Female Recipients With Male Donors Will be Computed With Corresponding Exact Binomial 95% Confidence Intervals. | The difference in DFS in recipient-donor combinations in which there is at least 1 KIR ligand mismatch versus those without a KIR ligand mismatch will be tested using log-rank test. | No data were collected or analyzed. | Posted | Up to 1 year |
|
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1 year
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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 | Treatment (Haploidentical Allogeneic HSCT) | Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28. Total-body irradiation: Undergo TBI Donor lymphocytes infusion (DLI): Undergo DLI Cyclophosphamide: Given IV Allogeneic hematopoietic stem cell transplantation (HSCT): Undergo haploidentical allogeneic HSCT Tacrolimus: Given IV Mycophenolate mofetil: Given IV | 3 | 4 | 4 | 4 | 4 | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| increased LFTs | Hepatobiliary disorders | Non-systematic Assessment |
| ||
| Colitis - infectious diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Fever | Immune system disorders | Non-systematic Assessment |
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| CMV reactivation | Immune system disorders | Non-systematic Assessment |
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| UTI | Renal and urinary disorders | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Acid reflux | Gastrointestinal disorders | Non-systematic Assessment |
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| Anxiety | Nervous system disorders | Non-systematic Assessment |
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| Arrhythmia | Cardiac disorders | Non-systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Awakening to Urinate | General disorders | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Blurred vision | Eye disorders | Non-systematic Assessment |
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| C. Difficile | Infections and infestations | Non-systematic Assessment |
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| CMV reactivation | Immune system disorders | Non-systematic Assessment |
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| Constipation | Reproductive system and breast disorders | Non-systematic Assessment |
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| Dehydration | General disorders | Non-systematic Assessment |
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| Depression | Nervous system disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Dizziness | General disorders | Non-systematic Assessment |
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| Dry Hands | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Dysuria | Renal and urinary disorders | Non-systematic Assessment |
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| Dysgeusia | General disorders | Non-systematic Assessment |
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| Electrolyte Abnormalities | General disorders | Non-systematic Assessment |
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| Elevated transaminase | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Fatigue | General disorders | Non-systematic Assessment |
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| Fever | Infections and infestations | Non-systematic Assessment |
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| Fluid overload | General disorders | Non-systematic Assessment |
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| GERD | Gastrointestinal disorders | Non-systematic Assessment |
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| Glaucoma | Eye disorders | Non-systematic Assessment |
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| Hallucinations | Nervous system disorders | Non-systematic Assessment |
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| Hives - related to injection | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Hyperpigmentation | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Hypertension | Cardiac disorders | Non-systematic Assessment |
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| Hypotension | Cardiac disorders | Non-systematic Assessment |
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| Increased Creatinine | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Increased LFTs | Renal and urinary disorders | Non-systematic Assessment |
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| Indigestion | Gastrointestinal disorders | Non-systematic Assessment |
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| Insomnia | Nervous system disorders | Non-systematic Assessment |
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| Iron overload | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Itching | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Knee pain | General disorders | Non-systematic Assessment |
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| Swelling | General disorders | Non-systematic Assessment |
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| Lightheadedness | General disorders | Non-systematic Assessment |
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| Mucositis | General disorders | Non-systematic Assessment |
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| Numbness | Nervous system disorders | Non-systematic Assessment |
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| Parotiditis | General disorders | Non-systematic Assessment |
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| Pericatheter Thrombus | Renal and urinary disorders | Non-systematic Assessment |
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| Pruitis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Pronatriuretic Peptide elevated | General disorders | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Rigors | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Runny nose | General disorders | Non-systematic Assessment |
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| Short term memory loss | Nervous system disorders | Non-systematic Assessment |
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| Sweating | General disorders | Non-systematic Assessment |
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| Swollen hands | General disorders | Non-systematic Assessment |
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| SOB | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Stomach cramping | Gastrointestinal disorders | Non-systematic Assessment |
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| Tachycardia | Cardiac disorders | Non-systematic Assessment |
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| Tachypenea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Trouble sleeping | General disorders | Non-systematic Assessment |
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| Twitching | Nervous system disorders | Non-systematic Assessment |
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| Urinary incontinence | Renal and urinary disorders | Non-systematic Assessment |
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| Watery Eyes | Eye disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Neal Flomenberg | Sidney Kimmel Cancer Center at Thomas Jefferson University | 215 955-0182 | dolores.gross@jefferson.edu |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D014916 | Whole-Body Irradiation |
| D003520 | Cyclophosphamide |
| D016559 | Tacrolimus |
| D009173 | Mycophenolic Acid |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D018942 | Macrolides |
| D007783 | Lactones |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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