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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-00315 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| P01HL036444 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| National Cancer Institute (NCI) | NIH |
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This phase II trial is studying how well giving treosulfan together with fludarabine phosphate and total-body irradiation followed by donor stem cell transplant works in treating patients with high-risk acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia. Giving chemotherapy, such as treosulfan and fludarabine phosphate, and total-body irradiation before a donor bone marrow or peripheral blood 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. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate before and after transplant may stop this from happening
PRIMARY OBJECTIVES:
I. Decrease the incidence of relapse to < 15% at 6 month post transplant in patients with high risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transplanted from related or unrelated donors, without unacceptably increasing toxicity (10% non-relapse mortality [NRM] at 6 months).
SECONDARY OBJECTIVES:
I. Evaluate the incidence of NRM at 180 days and 1 year after hematopoietic cell transplantation (HCT).
II. Evaluate overall survival (OS) and relapse-free survival (RFS). III. Incidence of grades II-IV acute graft-versus-host disease (GVHD). IV. Incidence of chronic GVHD. V. Donor chimerism on days +28 and +100.
OUTLINE:
CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally (PO) twice daily (BID) on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
After completion of study treatment, patients are followed up periodically.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (allogeneic transplantation) | Experimental | CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| treosulfan | Drug | Given IV |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Relapse Incidence | At 6 months | |
| Non Relapse Mortality (NRM) Incidence | Cumulative incidence of NRM at 6 months. NRM includes all deaths without relapse or disease progression. | At 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Non Relapse Mortality Incidence | 1 year after HCT | |
| Overall Survival (OS) | at 2 years | |
| Relapse-free Survival |
Not provided
Inclusion Criteria:
Acute myeloid leukemia (AML):
Myelodysplastic syndrome (MDS)
Other myeloid malignancies as chronic myelogenous leukemia (CML), CML accelerated phase, CML blast crisis, chronic myelomonocytic leukemia (CMML) (to be approved by patient care conference [PCC])
With Karnofsky Index or Lansky Play-Performance Scale > 70% on pre-transplant evaluation
Able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)
Previous autologous or allogeneic HCT is allowed
Donors must be:
Acute lymphoblastic leukemia (ALL): all ALL patients not eligible for other protocols
Exclusion Criteria:
Receiving umbilical cord blood
With impaired cardiac function as evidenced by ejection fraction < 35% or cardiac insufficiency requiring treatment or symptomatic coronary artery disease
With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) < 70 mm Hg and diffusing capacity of the lung for carbon monoxide (DLCO) < 70% of predicted or pO2 < 80 mm Hg and DLCO < 60% of predicted; or receiving supplementary continuous oxygen
With impaired renal function as evidenced by creatinine-clearance < 50% for age, weight, height or serum creatinine > 2x upper normal limit or dialysis-dependent
With hepatic dysfunction as evidenced by total bilirubin or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.0 x upper normal limit or evidence of synthetic dysfunction or severe cirrhosis
With active infectious disease requiring deferral of conditioning, as recommended by an Infectious Disease specialist
With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis because of possible risk of lethal infection when treated with immunosuppressive therapy
With central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiating conditioning (day -6)
With life expectancy severely limited by diseases other than malignancy
Women who are pregnant or lactating because of possible risk to the fetus or infant
With known hypersensitivity to treosulfan and/or fludarabine
Receiving another experimental drug within 4 weeks before initiation of conditioning (day -6)
Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent
Ineligible donors will be those:
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| Name | Affiliation | Role |
|---|---|---|
| Boglarka Gyurkocza | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado | Denver | Colorado | 80217-3364 | United States | ||
| Oregon Health and Science University |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Allogeneic Transplantation) | CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| fludarabine phosphate | Drug | Given IV |
|
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| total-body irradiation | Radiation | Low dose starting at 2Gy |
|
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| peripheral blood stem cell transplantation | Procedure | Given IV per institutional standard practice |
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| tacrolimus | Drug | Given IV or PO |
|
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| allogeneic bone marrow transplantation | Procedure | Given IV per institutional standard practice |
|
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| allogeneic hematopoietic stem cell transplantation | Procedure | Given IV per institutional standard practice |
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| methotrexate | Drug | Given IV |
|
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| at 2 years |
| Incidence of Grades II-IV Acute GVHD | at 6 months |
| Incidence of Chronic GVHD | at 6 months |
| Median Donor CD3 + T Lymphocyte Chimerism in Peripheral Blood | Donor chimerism was evaluated in peripheral blood T cells | Day 28 after HCT |
| Portland |
| Oregon |
| 97239 |
| United States |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Allogeneic Transplantation) | CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6 and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: 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 | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | 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 | Relapse Incidence | Posted | Count of Participants | Participants | At 6 months |
|
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| ||||||||||||||||||||||||||||
| Primary | Non Relapse Mortality (NRM) Incidence | Cumulative incidence of NRM at 6 months. NRM includes all deaths without relapse or disease progression. | Posted | Count of Participants | Participants | At 6 months |
|
| ||||||||||||||||||||||||||||
| Secondary | Non Relapse Mortality Incidence | Posted | Count of Participants | Participants | 1 year after HCT |
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| |||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | Posted | Count of Participants | Participants | at 2 years |
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| Secondary | Relapse-free Survival | Posted | Count of Participants | Participants | at 2 years |
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| |||||||||||||||||||||||||||||
| Secondary | Incidence of Grades II-IV Acute GVHD | Posted | Count of Participants | Participants | at 6 months |
|
| |||||||||||||||||||||||||||||
| Secondary | Incidence of Chronic GVHD | Posted | Count of Participants | Participants | at 6 months |
|
| |||||||||||||||||||||||||||||
| Secondary | Median Donor CD3 + T Lymphocyte Chimerism in Peripheral Blood | Donor chimerism was evaluated in peripheral blood T cells | Posted | Median | Full Range | percentage of T cells | Day 28 after HCT |
|
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Toxicities Before Day 100
Toxicities documented per Common Terminology Criteria for Adverse Events (CTCAE) v3.0
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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 (Allogeneic Transplantation) | CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6 and 11. treosulfan: Given IV fludarabine phosphate: Given IV total-body irradiation: Low dose starting at 2Gy peripheral blood stem cell transplantation: Given IV per institutional standard practice tacrolimus: Given IV or PO allogeneic bone marrow transplantation: Given IV per institutional standard practice allogeneic hematopoietic stem cell transplantation: Given IV per institutional standard practice methotrexate: Given IV | 21 | 96 | 17 | 96 | 68 | 96 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mucositis | Gastrointestinal disorders |
| |||
| Bacterial/sepsis | Infections and infestations |
| |||
| Heart failure | Cardiac disorders |
| |||
| Gut GVHD | Gastrointestinal disorders |
| |||
| Sepsis | Infections and infestations |
| |||
| VRE bacteremia/sepsis | Infections and infestations |
| |||
| Disseminated toxoplasmosis | Infections and infestations |
| |||
| Enterococcal bacteremia/VRE | Infections and infestations |
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| CMV pneumonia | Infections and infestations |
| |||
| Aspirgillus | Infections and infestations |
| |||
| Hypotension | Cardiac disorders |
| |||
| Hyperglycemia | Metabolism and nutrition disorders |
| |||
| Acute respiratory distress syndrome (ARDS) | Respiratory, thoracic and mediastinal disorders |
| |||
| Hypoxia/resp failure | Respiratory, thoracic and mediastinal disorders |
| |||
| Pneumonitis | Respiratory, thoracic and mediastinal disorders |
| |||
| Intubated secondary to DAH | Respiratory, thoracic and mediastinal disorders |
| |||
| Respiratory failure/intubated | Respiratory, thoracic and mediastinal disorders |
| |||
| Cardiac arrythmia | Respiratory, thoracic and mediastinal disorders |
| |||
| Pul.Edema | Respiratory, thoracic and mediastinal disorders |
| |||
| Pneumonia | Respiratory, thoracic and mediastinal disorders |
| |||
| Bilirubin | Hepatobiliary disorders |
| |||
| Liver failure | Hepatobiliary disorders |
| |||
| AST 2680 | Hepatobiliary disorders |
| |||
| Hypoglycemia w/seizures | Metabolism and nutrition disorders |
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| Hyponatremia | Metabolism and nutrition disorders |
| |||
| Diffuse alveolar hemorrhage | Respiratory, thoracic and mediastinal disorders |
| |||
| Kidney rejection - pre-existing hx kidney transplant | Renal and urinary disorders |
| |||
| Renal failure/dialysis | Renal and urinary disorders |
| |||
| Renal failure | Renal and urinary disorders |
| |||
| Apnea | Psychiatric disorders |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mucositis | Gastrointestinal disorders |
| |||
| Mucosi | Gastrointestinal disorders |
| |||
| Infections | Infections and infestations |
| |||
| Deep vein thrombosis | Blood and lymphatic system disorders |
| |||
| Fatigue | General disorders |
| |||
| Adrenal insufficiency | General disorders |
| |||
| Hyperglycemia | Metabolism and nutrition disorders |
| |||
| Retinal central vein occlusion | Eye disorders |
| |||
| Dehydration | General disorders |
| |||
| Proximal myopathy | General disorders |
| |||
| Steroid induced DM | General disorders |
| |||
| LE weakness/deconditioning | General disorders |
| |||
| Fall | General disorders |
| |||
| Nausea | Gastrointestinal disorders |
| |||
| Vomiting | Gastrointestinal disorders |
| |||
| Diarrhea | Gastrointestinal disorders |
| |||
| Diverticulitis | Gastrointestinal disorders |
| |||
| Anorexia | Gastrointestinal disorders |
| |||
| Other | Gastrointestinal disorders |
| |||
| Pain | Musculoskeletal and connective tissue disorders |
| |||
| Abdominal pain | Gastrointestinal disorders |
| |||
| Neuropathic leg pain | Nervous system disorders |
| |||
| Atrial Fibrillation | Cardiac disorders |
| |||
| Edema | Cardiac disorders |
| |||
| Hypotension | Cardiac disorders |
| |||
| LVEF 35% | Cardiac disorders |
| |||
| Sinus tachycardia | Cardiac disorders |
| |||
| Hypoxia | Respiratory, thoracic and mediastinal disorders |
| |||
| Pleural effusion | Respiratory, thoracic and mediastinal disorders |
| |||
| Dyspnea | Respiratory, thoracic and mediastinal disorders |
| |||
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders |
| |||
| Rash | Skin and subcutaneous tissue disorders |
| |||
| ALT/AST | Hepatobiliary disorders |
| |||
| ALT | Hepatobiliary disorders |
| |||
| AST | Hepatobiliary disorders |
| |||
| t.bili 4.2 | Hepatobiliary disorders |
| |||
| Bilirubin | Hepatobiliary disorders |
| |||
| Myalgia | Musculoskeletal and connective tissue disorders |
| |||
| Steroid myopathy | Musculoskeletal and connective tissue disorders |
| |||
| Elevated ferritin | Metabolism and nutrition disorders |
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| Hyperkalemia | Metabolism and nutrition disorders |
| |||
| GI bleed | Gastrointestinal disorders |
| |||
| Confusion | Psychiatric disorders |
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| Altered Mental Status | Psychiatric disorders |
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| Dysuria | Renal and urinary disorders |
| |||
| Acute renal failure/creatinine | Renal and urinary disorders |
| |||
| Creatinine | Renal and urinary disorders |
| |||
| Renal failure/acidosis | Renal and urinary disorders |
| |||
| Syncope | Nervous system disorders |
| |||
| Peripheral neuropathy | Nervous system disorders |
| |||
| Hallucinations | Psychiatric disorders |
| |||
| Posterior reversible encephalopathy syndrome (PRES) | Nervous system disorders |
| |||
| Malnutrition | General disorders |
| |||
| Thrombotic thrombocytopenic purpura (TTP) coagulation | Blood and lymphatic system disorders |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joachim Deeg | Fred Hutch/University of Washington Cancer Consortium | 206.667.5985 | jdeeg@fredhutch.org |
| ID | Term |
|---|---|
| D015465 | Leukemia, Myeloid, Accelerated Phase |
| D000013 | Congenital Abnormalities |
| D001752 | Blast Crisis |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D002471 | Cell Transformation, Neoplastic |
| D063646 | Carcinogenesis |
| D009385 | Neoplastic Processes |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C018404 | treosulfan |
| C042382 | fludarabine phosphate |
| D014916 | Whole-Body Irradiation |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| D016559 | Tacrolimus |
| D014180 | Transplantation |
| D008727 | Methotrexate |
| C015342 | merphos |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013514 | Surgical Procedures, Operative |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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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 |
|
| Unknown or Not Reported |
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