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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-01395 | Registry Identifier | NCI CTRP |
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The goal of this clinical research study is to learn if the combination of arsenic trioxide (ATO) with ATRA and possibly idarubicin is effective in treating patients with newly-diagnosed APL.
All-trans retinoic acid (ATRA) and ATO are designed to cause the APL cells to mature and function normally. Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of cells).
If you are found to be eligible to take part in this study, you will begin induction. During induction, you will receive ATRA, by mouth starting on Day 1. You will also receive ATO through a needle in your vein over 2 hours starting on Day 1. You will continue receiving the drugs every day until your bone marrow no longer shows APL cells.
If you had a high white blood cell count at screening, you will receive idarubicin through a needle in your vein over about 30 minutes one dose only on any day of Day 1 through 5.
During induction, blood (about 1-3 tablespoons) will be drawn every day during Week 1, and then 2 times a week after that. This blood will be drawn for routine tests.
During induction (about 21-28 days after beginning treatment), you will have a bone marrow aspirate to check the status of the disease. This may be performed more often if the doctor thinks it is needed.
If you achieve a complete remission during the induction phase, you will continue to the maintenance phase. During the maintenance phase, you will receive ATO by vein over 2 hours Monday-Friday for 4 weeks. After the 4 weeks of receiving the study drug, you will have a 4-week period "off" (when no study drug is given). ATRA is given by mouth every day for 2 weeks. This 2 weeks is followed by 2 additional weeks when no study drug will be given. You will continue to take ATRA until treatment with ATO is complete.
During maintenance, blood (about 1-3 tablespoons) will be drawn before every 4-week cycle of ATO, and then every week for routine tests. You will also have an ECG before every 4 week cycle when you take ATO.
If you do not achieve a complete remission during induction you will be taken off study.
If at any point during the study your white blood cell count rises above 10,000, you will receive idarubicin by vein over 30 minutes.
You will remain in the hospital for about the first 7 days of induction. After that, you must remain in Houston for the next 3-4 weeks. Once in the maintenance phase, you may be treated at home, but must return to M. D. Anderson for study visits.
After maintenance is complete, you will have follow-up visits for an additional 2 years. If at any time during the active study or follow-up the disease gets worse or intolerable side effects occur, you will be taken off the study.
If you had a low or high white blood cell count when you joined the study, you will have follow-up visits every 3 months for 2 years. At these visits, blood (about 1 tablespoon) will be drawn for routine tests and you will have a bone marrow aspirate.
This is an investigational study. Idarubicin, ATRA and ATO are FDA approved and commercially available. However, their use in this study and in this combination is considered investigational. Its use in APL patients is investigational. Up to 80 patients will take part in this multicenter study. All will be enrolled at M. D. Anderson.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Induction ATRA + ATO + Idarubicin | Experimental | All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) ATRA 45 mg/m2 daily by mouth beginning day 1; ATO 0.15 mg/kg by vein daily beginning on day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days starting on day 1. |
|
| Maintenance | Experimental | All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) ATO 0.15 mg/kg by vein over 2 hours Monday-Friday for 4 weeks, then a 4-week break. ATRA 45 mg/m2 by mouth every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete. |
|
| Induction ATRA + ATO + GO | Experimental | All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) + Gemtuzumab Ozogamicin (GO) ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1; ATO 0.15 mg/kg IV daily beginning on day 1; GO 9 mg/m2 on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1. Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| All-Trans Retinoic Acid (ATRA) | Drug | Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Complete Response (CR) Rate | Response defined as CR (marrow with <5% blasts and no abnormal promyelocytes together with neutrophil count >1000 and platelet count >100,000) and toxicity as Acute promyelocytic leukemia (APL) differentiation syndrome, arrhythmia, peripheral neuropathy. Bone marrow aspirate performed to check the status of the disease. | 1 month, up to day 85 of treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Farhad Ravandi-Kashani, MD | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
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| Label | URL |
|---|---|
| University of Texas MD Anderson Cancer Center Website | View source |
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Pfizer withdrew gemtuzumab ozogamycin (GO) from market based Food & Drug Administration recommendation. As such, protocol modified to Idarubicin Day 1 of induction in high-risk participants & in low risk participants with rising white blood count (WBC), Idarubicin administered to low-risk patients in whom WBC >10,000 after initiation of ATRA + ATO.
Recruitment Period: December 5, 2006 to April 3, 2012. All recruitment done at The University of Texas MD Anderson Cancer Center.
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| ID | Title | Description |
|---|---|---|
| FG000 | ATRA + ATO: Low Risk (WBC<10,000) | All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO): Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg by vein (IV) daily beginning day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. Methylprednisolone 500 mg daily for 5 days followed by rapid taper starting on day 1 Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) as needed for WBC>10,000. 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date. Post CR 1.) ATO 0.15 mg/kg IV for 5 of every 7 days on each of weeks 1-4 (course 2), 9-12 (course 3), 17-20 (course 4), and 25-28 (course 5) (thus 4 courses). 2.) Oral ATRA 45 mg/m2 daily on a "2-weeks on -2-weeks off" basis until therapy with ATO completed. |
| FG001 | ATRA+ATO+IDA: High Risk (WBC >10,000) | Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg IV daily beginning day 1; Idarubicin (IDA) 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. ATRA Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; and ATO: Induction: 0.15 mg/kg daily IV beginning day 1. Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date. |
| FG002 | ATO+ATRA+GO | ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1 ATO 0.15 mg/kg IV daily beginning on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1 GO 9 mg/m2 on day 1 of induction Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed. Post-CR treatment ATO 0.15 mg/kg IV over 2 hours Monday-Friday for 4 weeks, then 4-week break. Oral ATRA 45 mg/m2 every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ATRA + ATO: Low Risk (WBC<10,000) | All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO): Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg by vein (IV) daily beginning day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. Methylprednisolone 500 mg daily for 5 days followed by rapid taper starting on day 1 Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) as needed for WBC>10,000. 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date. Post CR 1.) ATO 0.15 mg/kg IV for 5 of every 7 days on each of weeks 1-4 (course 2), 9-12 (course 3), 17-20 (course 4), and 25-28 (course 5) (thus 4 courses). 2.) Oral ATRA 45 mg/m2 daily on a "2-weeks on -2-weeks off" basis until therapy with ATO completed. |
| 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 |
| 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 | Complete Response (CR) Rate | Response defined as CR (marrow with <5% blasts and no abnormal promyelocytes together with neutrophil count >1000 and platelet count >100,000) and toxicity as Acute promyelocytic leukemia (APL) differentiation syndrome, arrhythmia, peripheral neuropathy. Bone marrow aspirate performed to check the status of the disease. | Of the 57 participants treated on the ATRA + ATO: Low Risk treatment arm, 56 participants were evaluable for response. | Posted | Count of Participants | Participants | 1 month, up to day 85 of treatment |
|
Up to 7 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 | ATRA + ATO: Low Risk (WBC<10,000) | All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO): Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg by vein (IV) daily beginning day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. Methylprednisolone 500 mg daily for 5 days followed by rapid taper starting on day 1 Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) as needed for WBC>10,000. 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date. Post CR 1.) ATO 0.15 mg/kg IV for 5 of every 7 days on each of weeks 1-4 (course 2), 9-12 (course 3), 17-20 (course 4), and 25-28 (course 5) (thus 4 courses). 2.) Oral ATRA 45 mg/m2 daily on a "2-weeks on -2-weeks off" basis until therapy with ATO completed. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendectomy | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Farhad Ravandi-Kashani, Professor, Leukemia | The University of Texas (UT) MD Anderson Cancer Center | 7137927734 | fravandi@mdanderson.org |
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| ID | Term |
|---|---|
| D015473 | Leukemia, Promyelocytic, Acute |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D014212 | Tretinoin |
| D000077237 | Arsenic Trioxide |
| D015255 | Idarubicin |
| D000079982 | Gemtuzumab |
| ID | Term |
|---|---|
| D014801 | Vitamin A |
| D012176 | Retinoids |
| D002338 | Carotenoids |
| D011090 | Polyenes |
| D000475 |
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| Arsenic Trioxide (ATO) | Drug | Induction: 0.15 mg/kg daily IV beginning day 1 |
|
| Idarubicin | Drug |
|
|
|
| Gemtuzumab Ozogamicin | Drug | Induction: 9 mg/m2 on day 1 of induction |
|
| BG001 | ATRA+ATO+IDA: High Risk (WBC >10,000) | Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg IV daily beginning day 1; Idarubicin (IDA) 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. ATRA Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; and ATO: Induction: 0.15 mg/kg daily IV beginning day 1. Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date. |
| BG002 | ATO+ATRA+GO | Induction ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1 ATO 0.15 mg/kg IV daily beginning on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1 GO 9 mg/m2 on day 1 of induction Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed. Post-CR treatment ATO 0.15 mg/kg IV over 2 hours Monday-Friday for 4 weeks, then 4-week break. Oral ATRA 45 mg/m2 every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | ATRA+ATO+IDA: High Risk (WBC >10,000) | Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg IV daily beginning day 1; Idarubicin (IDA) 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. ATRA Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; and ATO: Induction: 0.15 mg/kg daily IV beginning day 1. Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date. |
| OG002 | ATO+ATRA+GO | Induction ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1 ATO 0.15 mg/kg IV daily beginning on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1 GO 9 mg/m2 on day 1 of induction Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed. Post-CR treatment ATO 0.15 mg/kg IV over 2 hours Monday-Friday for 4 weeks, then 4-week break. Oral ATRA 45 mg/m2 every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete. |
|
|
| 1 |
| 57 |
| 22 |
| 57 |
| 5 |
| 57 |
| EG001 | ATRA+ATO+IDA: High Risk (WBC >10,000) | Oral ATRA 45 mg/m2 daily beginning day 1; ATO 0.15 mg/kg IV daily beginning day 1; Idarubicin (IDA) 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days. ATRA Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1; and ATO: Induction: 0.15 mg/kg daily IV beginning day 1. Idarubicin: 1) 12 mg/m2 one dose only (day 1 to 5 of induction) 2) If ATRA or ATO discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses administered once every 4- 5 weeks until 28 weeks elapsed from Complete Recovery date. | 0 | 5 | 4 | 5 | 0 | 5 |
| EG002 | ATO+ATRA+GO | Induction ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1 ATO 0.15 mg/kg IV daily beginning on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1 GO 9 mg/m2 on day 1 of induction Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed. Post-CR treatment ATO 0.15 mg/kg IV over 2 hours Monday-Friday for 4 weeks, then 4-week break. Oral ATRA 45 mg/m2 every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete. | 1 | 16 | 4 | 16 | 1 | 16 |
| Cardiac Troponin I | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chest Pain | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Depressed level of Consciousness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Elevated Transaminases | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Elevated Amylase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Elevated Creatinine | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Elevated Lipase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headache | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemoptysis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hernia Repair | Surgical and medical procedures | CTCAE (3.0) | Systematic Assessment |
|
| Hyperbilirubinemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Left Ventricular Diastolic Dysfunction | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Death | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea/Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Peripharal Neuropathy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Prolonged QTc interval | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Renal Insufficiency | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Retinoic acid syndrome | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Sensory Neuropathy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D009369 |
| Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| Alkenes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D053138 | Cyclohexenes |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D013729 | Terpenes |
| D004224 | Diterpenes |
| D010860 | Pigments, Biological |
| D001685 | Biological Factors |
| D001152 | Arsenicals |
| D007287 | Inorganic Chemicals |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D000080084 | Calicheamicins |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |