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| ID | Type | Description | Link |
|---|---|---|---|
| MT2012-04 | Other Identifier | Blood and Marrow Transplantation Program |
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| Name | Class |
|---|---|
| Mayo Clinic | OTHER |
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This is a Phase II therapeutic trial combining Decitabine days 1-5 with oral Vorinostat twice daily days 6-15 followed by a single infusion of CD3-/CD19- enriched donor natural killer (NK) cells on day 17 and a short course of Interleukin-2 (IL-2) to facilitate NK cell survival and expansion. Two courses of treatment will be given separated by 6-8 weeks. The intent is to administer all treatment in the outpatient setting.
A single donor apheresis will be collected on day 15 of cycle 1, enriched for NK cells with the large scale CliniMacs device (Miltenyi) and activated by overnight incubation with IL-2. After washing, the final NK cell product will be divided in two, with half given fresh on day 17 of course #1 and half stored frozen until day 17 of course #2.
Clinical response will be formally assessed 4-6 weeks after the start of 2nd course based on International Working Group (IWG) criteria; however, bone marrow evaluations will be completed to assess for any sign of significant disease progression between cycle 1 and 2.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients With High Risk MDS | Experimental | Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Decitabine | Drug | administered intravenous (IV), 10 mg/m^2/day over 1 hour on days 1-5. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Number of Patients Who Achieved a Clinical Response | Clinical response includes: Complete Response (less than 5% myeloblasts present in the bone marrow and in the peripheral blood a hemoglobin of at least 11g/dl, platelets of at least 100 X 10E9/L, neutrophils of at least 1.0 X 10E9/L, and blasts 0%); Partial Response (all Complete Response criteria if previously abnormal except bone marrow myeloblasts are decreased by more than 50% over pre-treatment, but still greater than 5%); and hematologic improvement (a hemoglobin increase of greater than 1.5g/dl or decreased red blood cell transfusions by at least 4 per 8 week period, a platelet increase of more than 30 X 10E9/L for patients with a baseline of more than 20 X 10E9/L or an increase by 100% for those with a baseline of less than 20 X 10E9/L, and a neutrophil increase of at least 100% and an absolute increase of greater than 0.5 X 10E9/L. | After 2 Courses of Treatment (Approx. 3 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Who Experienced Grade 3 or Higher Non-hematologic Adverse Events | Adverse events (AEs) will be graded using Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Non-hematologic adverse events are defined as untoward medical occurrences associated with the use of a study drug whether or not considered study drug related, excluding those events involving white blood cells, neutrophils, red blood cells or platelets. In general, grade 3 AEs are defined as 1) being severe or medically significant but,not immediately life-threatening; 2) requiring hospitalization or prolongation of hospitalization; 3) disabling; or 4) limiting self care activities. Grade 4 AEs are defined as 1) having life-threatening consequences; or 2) requiring urgent intervention. Grade 5 AEs are defined as causing death related to an adverse event. |
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Inclusion Criteria:
Diagnosis of high risk myelodysplastic (MDS) that meets one of the following disease classifications and is requiring treatment:
Patients may be untreated or have had a maximum of 2 cycles of hypomethylating agents (azacitidine or decitabine) without evidence of treatment failure as defined by progression to more advanced MDS Who classification or AML. Patients must not have received treatment for their MDS within 4 weeks of beginning the trial. Treatments allowed prior to that time include azacitidine or decitabine and hematopoietic growth factors. No prior AML-like induction therapy allowed.
Age ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Available related HLA-haploidentical NK cell donor by at least Class I serologic typing at the A&B locus
Have acceptable organ function within 14 days of enrollment
Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to the natural killer (NK) cell infusion
Women of child bearing potential must agree to use effective methods of contraception
Voluntary written consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Erica Warlick, M.D. | Masonic Cancer Center, University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Masonic Cancer Center, University of Minnesota | Minneapolis | Minnesota | 55455 | United States | ||
| Mayo Clinic |
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| ID | Title | Description |
|---|---|---|
| FG000 | Patients With High Risk MDS | Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17 |
| 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 28, 2014 |
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| Vorinostat | Drug | 200 mg by mouth (PO) twice a day on days 6-15 |
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| Interleukin-2 | Biological | 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 |
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| Natural killer (NK) cells | Other | infusion intravenously (IV) over 15 to 60 minutes day 17 |
|
| Day 1 through Month 3 |
| Number of Patients Who Became Transfusion Independent | 4-6 Months Post Start of Cycle 1 |
| Number of Patients Who Had Natural Killer (NK) Cell Expansion | NK cell expansion is defined as the presence of donor NK cells in the recipient at Day 8 post NK cell infusion. | After Cycle 2 (approx. 3 months) |
| Overall Survival | Patients alive at 1 year. | 1 Year |
| Rochester |
| Minnesota |
| 55901 |
| United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Patients With High Risk MDS | Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (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 | The Number of Patients Who Achieved a Clinical Response | Clinical response includes: Complete Response (less than 5% myeloblasts present in the bone marrow and in the peripheral blood a hemoglobin of at least 11g/dl, platelets of at least 100 X 10E9/L, neutrophils of at least 1.0 X 10E9/L, and blasts 0%); Partial Response (all Complete Response criteria if previously abnormal except bone marrow myeloblasts are decreased by more than 50% over pre-treatment, but still greater than 5%); and hematologic improvement (a hemoglobin increase of greater than 1.5g/dl or decreased red blood cell transfusions by at least 4 per 8 week period, a platelet increase of more than 30 X 10E9/L for patients with a baseline of more than 20 X 10E9/L or an increase by 100% for those with a baseline of less than 20 X 10E9/L, and a neutrophil increase of at least 100% and an absolute increase of greater than 0.5 X 10E9/L. | Posted | Count of Participants | Participants | After 2 Courses of Treatment (Approx. 3 months) |
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| |||||||||||||||||||||||||||
| Secondary | Number of Patients Who Experienced Grade 3 or Higher Non-hematologic Adverse Events | Adverse events (AEs) will be graded using Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Non-hematologic adverse events are defined as untoward medical occurrences associated with the use of a study drug whether or not considered study drug related, excluding those events involving white blood cells, neutrophils, red blood cells or platelets. In general, grade 3 AEs are defined as 1) being severe or medically significant but,not immediately life-threatening; 2) requiring hospitalization or prolongation of hospitalization; 3) disabling; or 4) limiting self care activities. Grade 4 AEs are defined as 1) having life-threatening consequences; or 2) requiring urgent intervention. Grade 5 AEs are defined as causing death related to an adverse event. | Posted | Count of Participants | Participants | Day 1 through Month 3 |
| |||||||||||||||||||||||||||||
| Secondary | Number of Patients Who Became Transfusion Independent | 7 of the 9 patients were not evaluable for this outcome measure - 5 went on to stem cell transplant and 2 died before reaching the 4-6 month post start of cycle 1 milestone.This left 2 evaluable patients for the outcome measure, and thus this endpoint is not informative due to lack of evaluable patients. | Posted | Count of Participants | Participants | 4-6 Months Post Start of Cycle 1 |
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| Secondary | Number of Patients Who Had Natural Killer (NK) Cell Expansion | NK cell expansion is defined as the presence of donor NK cells in the recipient at Day 8 post NK cell infusion. | Posted | Count of Participants | Participants | After Cycle 2 (approx. 3 months) |
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| Secondary | Overall Survival | Patients alive at 1 year. | Posted | Count of Participants | Participants | 1 Year |
|
|
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 | Patients With High Risk MDS | Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17 | 7 | 9 | 6 | 9 | 9 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | Systematic Assessment |
| ||
| Renal Colic | Renal and urinary disorders | Systematic Assessment |
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| Febrile Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Ear Pain | Ear and labyrinth disorders | Systematic Assessment |
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| Otomastoiditis | Ear and labyrinth disorders | Systematic Assessment |
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| Upper Respiratory Infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Infection, Source Unknown | Infections and infestations | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chills | General disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Creatinine Increased | Investigations | Systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Edema, NOS | General disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Febrile Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Fever | General disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Hypertension | Vascular disorders | Systematic Assessment |
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| Hypotension | Vascular disorders | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Infusion Related Reaction | General disorders | Systematic Assessment |
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| Injection Site Reaction | General disorders | Systematic Assessment |
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| Itchy Nose | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Nasal Drainage | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Para-Influenza | Infections and infestations | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| White Blood Cell Decreased | Investigations | Systematic Assessment |
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| Neutrophil Count Decreased | Investigations | Systematic Assessment |
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| Platelet Count Decreased | Investigations | Systematic Assessment |
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| Bacteremia | Infections and infestations | Systematic Assessment |
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| Cellulitis, Toe | Infections and infestations | Systematic Assessment |
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| Alanine Aminotransferase Increased | Investigations | Systematic Assessment |
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| Aspartate Aminotransferase Increased | Investigations | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
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| Blood Bilirubin Increased | Investigations | Systematic Assessment |
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| Cholecystitis | Hepatobiliary disorders | Systematic Assessment |
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| Cholesterol High | Investigations | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Ear Pain | Ear and labyrinth disorders | Systematic Assessment |
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| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Edema, Ankle | General disorders | Systematic Assessment |
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| Pain, Toe | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Renal Calculi | Renal and urinary disorders | Systematic Assessment |
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| Renal Colic | Renal and urinary disorders | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Erica Warlick | Masonic Cancer Center, University of Minnesota | 612-625-5467 | ewarlick@umn.edu |
| May 14, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000077209 | Decitabine |
| D000077337 | Vorinostat |
| D007376 | Interleukin-2 |
| D002452 | Cell Count |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D000813 | Anilides |
| D000577 | Amides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D008222 | Lymphokines |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D002468 | Cell Physiological Phenomena |
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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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