Comparison of Two Combination Chemotherapy Regimens With... | NCT00059839

NCT00059839

ID	Type	Description	Link
CDR0000298777	Other Identifier	Clinical Trials.gov
COG-ANHL0131	Other Identifier	Children's Oncology Group

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

OBJECTIVES:

Compare the efficacy of a consolidation chemotherapy regimen comprising doxorubicin and prednisone in combination with vincristine vs vinblastine, in terms of event-free survival, in patients with advanced anaplastic large cell lymphoma.
Compare overall survival of patients treated with these regimens.
Compare the toxic effects of these regimens in these patients.
Correlate biological tumor characteristics and outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study.

Patients are randomized at enrollment to receive either Standard APO regimen or a consolidation regimen including vinblastine (VBL).

Induction therapy: All Patients receive doxorubicin IV over 15 minutes on days 1 and 22; vincristine IV on days 1, 8, 15, 22, and 29; oral prednisone 3 times daily on days 1-28; and intrathecal (IT) methotrexate on days 1, 8, and 22 (patients with central nervous system (CNS) disease at diagnosis receive additional methotrexate IT on days 15, 29, and 36).

Patients undergo restaging after Induction such that consolidation therapy is started on day 43. All patients with complete response (CR), complete response unconfirmed (CRu) or partial response (PR) proceed to Consolidation based on CT or MRI scans at the end of induction (week 6). All other patients will be removed from protocol therapy and will be followed until they meet the criteria for off study. Follow-up data will be required unless consent is withdrawn.

Standard APO (Arm I): Patients receive course-specific regimens without vinblastine.
- Courses 1-3: Patients receive doxorubicin IV over 15 minutes, vincristine IV, and methotrexate IT on day 1 and oral prednisone three times daily and oral mercaptopurine once daily on days 1-5.
- Courses 4-5: Patients receive doxorubicin, vincristine, prednisone, and mercaptopurine as in courses 1-3.
- Courses 6-15: Patients receive vincristine, prednisone, and mercaptopurine as in courses 1-3 and methotrexate IV on day 1.
Consolidation with vinblastine (Arm II): Patients receive course-specific regimens including vinblastine.
- Courses 1-3: Patients receive doxorubicin, methotrexate IT, prednisone, and mercaptopurine as in arm I and vinblastine IV over 1 minute on days 1, 8, and 15.
- Courses 4-5: Patients receive doxorubicin, prednisone, and mercaptopurine as in arm I and vinblastine as in arm II (courses 1-3).
- Courses 6-15: Patients receive prednisone and mercaptopurine as in arm I, vinblastine as in arm II (courses 1-3), and methotrexate IV on day 1.

In both arms and all courses, treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 200-250 patients (100-125 per treatment arm) will be accrued for this study within 5 years.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Standard APO with Vincristine (Arm I )	Experimental	In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.	Drug: doxorubicin hydrochloride Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: vincristine sulfate
Consolidation with Vinblastine	Experimental	In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV, methotrexate (age adjusted dosing) IT, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin hydrochloride (30 mg/m2) IV, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) as in arm II (courses 1-3). In courses 6-15, patients receive prednisone (120 mg/m2/day) and mercaptopurine (225 mg/m2) as in arm I, vinblastine sulfate (4 mg/m2) IV as in arm II (courses 1-3), and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.	Drug: doxorubicin hydrochloride Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: vinblastine sulfate

Name	Type	Description	Arm Group Labels	Other Names
doxorubicin hydrochloride	Drug	Given IV	Consolidation with Vinblastine Standard APO with Vincristine (Arm I )

Measure	Description	Time Frame
Event-free Survival (EFS)	Percentage of EFS patients. This is measured as the time from study entry until disease progression, disease recurrence, occurrence of a second malignant neoplasm, or death from any cause. To measure Event Free Survival, repeated one-sided logrank tests will be performed The upper critical values are based on the one-sided alpha-spending functions of t2 (alpha=0.05) and the lower critical values are based on testing the alternative hypothesis at 0.005 level.	From first enrollment up to 3 years.

Eligibility Module

Name	Affiliation	Role
Jacqueline Kraveka, DO	Medical University of South Carolina	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham		Birmingham	Alabama	35294	United States

PubMed Identifier	Type	Citation	Retractions
25156886	Derived	Alexander S, Kraveka JM, Weitzman S, Lowe E, Smith L, Lynch JC, Chang M, Kinney MC, Perkins SL, Laver J, Gross TG, Weinstein H. Advanced stage anaplastic large cell lymphoma in children and adolescents: results of ANHL0131, a randomized phase III trial of APO versus a modified regimen with vinblastine: a report from the children's oncology group. Pediatr Blood Cancer. 2014 Dec;61(12):2236-42. doi: 10.1002/pbc.25187. Epub 2014 Aug 23.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Standard (APO) With Vincristine (Arm I)	In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Standard (APO) With Vincristine (Arm I)	In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.
BG001	Consolidation (Includes Vinblastine) (Arm II)	In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV, methotrexate (age adjusted dosing) IT, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin hydrochloride (30 mg/m2) IV, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) as in arm II (courses 1-3). In courses 6-15, patients receive prednisone (120 mg/m2/day) and mercaptopurine (225 mg/m2) as in arm I, vinblastine sulfate (4 mg/m2) IV as in arm II (courses 1-3), and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG00062 BG00162 BG002124
Between 18 and 65 years

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00024 BG00127 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00010 BG0018 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00059 BG00152 BG002

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

Event-free Survival (EFS)

Percentage of EFS patients. This is measured as the time from study entry until disease progression, disease recurrence, occurrence of a second malignant neoplasm, or death from any cause. To measure Event Free Survival, repeated one-sided logrank tests will be performed The upper critical values are based on the one-sided alpha-spending functions of t2 (alpha=0.05) and the lower critical values are based on testing the alternative hypothesis at 0.005 level.

64 patients from Arm I were analyzed for this outcome measure, one patient was deemed ineligible. 61 patients from Arm II were analyzed for this outcome measure, three patients were deemed ineligible.

Posted

Number

95% Confidence Interval

percentage of participants

From first enrollment up to 3 years.

ID	Title	Description
OG000	Standard (APO) With Vincristine (Arm I)	In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.
OG001	Consolidation (Includes Vinblastine) (Arm II)	In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV, methotrexate (age adjusted dosing) IT, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin hydrochloride (30 mg/m2) IV, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) as in arm II (courses 1-3). In courses 6-15, patients receive prednisone (120 mg/m2/day) and mercaptopurine (225 mg/m2) as in arm I, vinblastine sulfate (4 mg/m2) IV as in arm II (courses 1-3), and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.

Units	Counts
Participants	OG00064 OG00161

Title

Denominators

Categories

Title	Measurements
	OG00074(61 to 84) OG00179(65 to 87)

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Standard (APO) With Vincristine (Arm I)	In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.			2	64	47	64
EG001	Consolidation (Includes Vinblastine) (Arm II)	In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV, methotrexate (age adjusted dosing) IT, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin hydrochloride (30 mg/m2) IV, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) as in arm II (courses 1-3). In courses 6-15, patients receive prednisone (120 mg/m2/day) and mercaptopurine (225 mg/m2) as in arm I, vinblastine sulfate (4 mg/m2) IV as in arm II (courses 1-3), and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.			4	61	52	61

Serious Adverse Events

Term	Organ System	Statistical Information
Anemia	Blood and lymphatic system disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
"Blood and lymphatic system disorders - Other"	Blood and lymphatic system disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Febrile neutropenia	Blood and lymphatic system disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Cardiac arrest	Cardiac disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
"Cardiac disorders - Other"	Cardiac disorders	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
Vomiting	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Death NOS	General disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Hepatic failure	Hepatobiliary disorders	EG0001 events1 affected64 at risk EG0011 events1 affected1 at risk
Activated partial thromboplastin time prolonged	Investigations	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
Aspartate aminotransferase increased	Investigations	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
CPK increased	Investigations	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Hypokalemia	Metabolism and nutrition disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
"Nervous system disorders - Other"	Nervous system disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Seizure	Nervous system disorders	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk

Other Adverse Events

Term	Organ System	Statistical Information
Anemia	Blood and lymphatic system disorders	EG00014 events14 affected64 at risk EG00124 events24 affected61 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Febrile neutropenia	Blood and lymphatic system disorders	EG0007 events7 affected64 at risk EG00118 events18 affected61 at risk
"Cardiac disorders - Other"	Cardiac disorders	EG0002 events2 affected64 at risk EG0010 events0 affected61 at risk
Conduction disorder	Cardiac disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Sinus tachycardia	Cardiac disorders	EG0000 events0 affected64 at risk EG0013 events3 affected61 at risk
Middle ear inflammation	Ear and labyrinth disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Blurred vision	Eye disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Cataract	Eye disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
"Eye disorders - Other"	Eye disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Abdominal pain	Gastrointestinal disorders	EG0004 events4 affected64 at risk EG0015 events5 affected61 at risk
Anal mucositis	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Colonic perforation	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Constipation	Gastrointestinal disorders	EG0005 events5 affected64 at risk EG0018 events8 affected61 at risk
Diarrhea	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0015 events5 affected61 at risk
Enterocolitis	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Esophageal pain	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Gastritis	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
"Gastrointestinal disorders - Other"	Gastrointestinal disorders	EG0002 events2 affected64 at risk EG0011 events1 affected61 at risk
Gingival pain	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0013 events3 affected61 at risk
Ileus	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Mucositis oral	Gastrointestinal disorders	EG0006 events6 affected64 at risk EG0017 events7 affected61 at risk
Nausea	Gastrointestinal disorders	EG0003 events3 affected64 at risk EG0018 events8 affected61 at risk
Oral pain	Gastrointestinal disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Pancreatitis	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Stomach pain	Gastrointestinal disorders	EG0001 events1 affected64 at risk EG0012 events2 affected61 at risk
Typhlitis	Gastrointestinal disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Vomiting	Gastrointestinal disorders	EG0001 events1 affected64 at risk EG00110 events10 affected61 at risk
Chills	General disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Edema limbs	General disorders	EG0000 events0 affected64 at risk EG0013 events3 affected61 at risk
Fatigue	General disorders	EG0003 events3 affected64 at risk EG0015 events5 affected61 at risk
Fever	General disorders	EG0004 events4 affected64 at risk EG0016 events6 affected61 at risk
Injection site reaction	General disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Irritability	General disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Non-cardiac chest pain	General disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Pain	General disorders	EG0003 events3 affected64 at risk EG0016 events6 affected61 at risk
Catheter related infection	Infections and infestations	EG0004 events4 affected64 at risk EG0011 events1 affected61 at risk
Gum infection	Infections and infestations	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
"Infections and infestations - Other"	Infections and infestations	EG0006 events6 affected64 at risk EG00120 events20 affected61 at risk
Laryngitis	Infections and infestations	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Lung infection	Infections and infestations	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Mucosal infection	Infections and infestations	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Otitis externa	Infections and infestations	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Otitis media	Infections and infestations	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Penile infection	Infections and infestations	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Pharyngitis	Infections and infestations	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Rhinitis infective	Infections and infestations	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Sepsis	Infections and infestations	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Skin infection	Infections and infestations	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
Upper respiratory infection	Infections and infestations	EG0002 events2 affected64 at risk EG0012 events2 affected61 at risk
Urinary tract infection	Infections and infestations	EG0002 events2 affected64 at risk EG0011 events1 affected61 at risk
Vaginal infection	Infections and infestations	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Fracture	Injury, poisoning and procedural complications	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
"Injury, poisoning and procedural complications - Other"	Injury, poisoning and procedural complications	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Vascular access complication	Injury, poisoning and procedural complications	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Activated partial thromboplastin time prolonged	Investigations	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Alanine aminotransferase increased	Investigations	EG00015 events15 affected64 at risk EG00126 events26 affected61 at risk
Aspartate aminotransferase increased	Investigations	EG0007 events7 affected64 at risk EG00116 events16 affected61 at risk
Blood bilirubin increased	Investigations	EG0002 events2 affected64 at risk EG0014 events4 affected61 at risk
Creatinine increased	Investigations	EG0001 events1 affected64 at risk EG0013 events3 affected61 at risk
GGT increased	Investigations	EG0003 events3 affected64 at risk EG0012 events2 affected61 at risk
INR increased	Investigations	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
"Investigations - Other"	Investigations	EG0002 events2 affected64 at risk EG0010 events0 affected61 at risk
Lipase increased	Investigations	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
Lymphocyte count decreased	Investigations	EG0002 events2 affected64 at risk EG0018 events8 affected61 at risk
Neutrophil count decreased	Investigations	EG00034 events34 affected64 at risk EG00147 events47 affected61 at risk
Platelet count decreased	Investigations	EG0006 events6 affected64 at risk EG0019 events9 affected61 at risk
Serum amylase increased	Investigations	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
Weight gain	Investigations	EG0002 events2 affected64 at risk EG0012 events2 affected61 at risk
Weight loss	Investigations	EG0000 events0 affected64 at risk EG0013 events3 affected61 at risk
White blood cell decreased	Investigations	EG00020 events20 affected64 at risk EG00131 events31 affected61 at risk
Acidosis	Metabolism and nutrition disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Anorexia	Metabolism and nutrition disorders	EG0003 events3 affected64 at risk EG0011 events1 affected61 at risk
Dehydration	Metabolism and nutrition disorders	EG0001 events1 affected64 at risk EG0012 events2 affected61 at risk
Hypercalcemia	Metabolism and nutrition disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Hyperglycemia	Metabolism and nutrition disorders	EG0008 events8 affected64 at risk EG0019 events9 affected61 at risk
Hyperkalemia	Metabolism and nutrition disorders	EG0000 events0 affected64 at risk EG0013 events3 affected61 at risk
Hypermagnesemia	Metabolism and nutrition disorders	EG0002 events2 affected64 at risk EG0012 events2 affected61 at risk
Hypernatremia	Metabolism and nutrition disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Hyperuricemia	Metabolism and nutrition disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	EG0003 events3 affected64 at risk EG0016 events6 affected61 at risk
Hypocalcemia	Metabolism and nutrition disorders	EG0005 events5 affected64 at risk EG00112 events12 affected61 at risk
Hypoglycemia	Metabolism and nutrition disorders	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
Hypokalemia	Metabolism and nutrition disorders	EG0007 events7 affected64 at risk EG00112 events12 affected61 at risk
Hypomagnesemia	Metabolism and nutrition disorders	EG0001 events1 affected64 at risk EG0013 events3 affected61 at risk
Hyponatremia	Metabolism and nutrition disorders	EG0004 events4 affected64 at risk EG0016 events6 affected61 at risk
Hypophosphatemia	Metabolism and nutrition disorders	EG0004 events4 affected64 at risk EG0016 events6 affected61 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
Avascular necrosis	Musculoskeletal and connective tissue disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Back pain	Musculoskeletal and connective tissue disorders	EG0002 events2 affected64 at risk EG0013 events3 affected61 at risk
Bone pain	Musculoskeletal and connective tissue disorders	EG0002 events2 affected64 at risk EG0011 events1 affected61 at risk
Chest wall pain	Musculoskeletal and connective tissue disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Muscle weakness upper limb	Musculoskeletal and connective tissue disorders	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
"Musculoskeletal and connective tissue disorder - Other, specify"	Musculoskeletal and connective tissue disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Neck pain	Musculoskeletal and connective tissue disorders	EG0001 events1 affected64 at risk EG0011 events1 affected61 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	EG0002 events2 affected64 at risk EG0011 events1 affected61 at risk
Tumor pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Cognitive disturbance	Nervous system disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Depressed level of consciousness	Nervous system disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Dizziness	Nervous system disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Dysgeusia	Nervous system disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Headache	Nervous system disorders	EG0002 events2 affected64 at risk EG0019 events9 affected61 at risk
Leukoencephalopathy	Nervous system disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Neuralgia	Nervous system disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Peripheral motor neuropathy	Nervous system disorders	EG0001 events1 affected64 at risk EG0016 events6 affected61 at risk
Peripheral sensory neuropathy	Nervous system disorders	EG0003 events3 affected64 at risk EG0017 events7 affected61 at risk
Seizure	Nervous system disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Agitation	Psychiatric disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Anxiety	Psychiatric disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Depression	Psychiatric disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Insomnia	Psychiatric disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Personality change	Psychiatric disorders	EG0001 events1 affected64 at risk EG0012 events2 affected61 at risk
Acute kidney injury	Renal and urinary disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Bladder spasm	Renal and urinary disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Cystitis noninfective	Renal and urinary disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Urinary frequency	Renal and urinary disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected64 at risk EG0010 events0 affected61 at risk
Apnea	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Cough	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected64 at risk EG0012 events2 affected61 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Pharyngeal mucositis	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
"Respiratory, thoracic and mediastinal disorders - Other"	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Alopecia	Skin and subcutaneous tissue disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Pain of skin	Skin and subcutaneous tissue disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Pruritus	Skin and subcutaneous tissue disorders	EG0001 events1 affected64 at risk EG0014 events4 affected61 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	EG0001 events1 affected64 at risk EG0013 events3 affected61 at risk
"Skin and subcutaneous tissue disorders - Other"	Skin and subcutaneous tissue disorders	EG0000 events0 affected64 at risk EG0012 events2 affected61 at risk
Skin ulceration	Skin and subcutaneous tissue disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Urticaria	Skin and subcutaneous tissue disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk
Hypertension	Vascular disorders	EG0001 events1 affected64 at risk EG0016 events6 affected61 at risk
Hypotension	Vascular disorders	EG0001 events1 affected64 at risk EG0014 events4 affected61 at risk
Thromboembolic event	Vascular disorders	EG0000 events0 affected64 at risk EG0011 events1 affected61 at risk

Ancestor Terms

ID	Term
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D013438	Sulfhydryl Compounds
D013457	Sulfur Compounds
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D014748	Vinca Alkaloids
D046948	Secologanin Tryptamine Alkaloids
D026121	Indole Alkaloids
D000470	Alkaloids
D007211	Indoles
D054836	Indolizidines
D007212	Indolizines

ID	Term
D008223	Lymphoma
D017728	Lymphoma, Large-Cell, Anaplastic

ID	Term
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D016399	Lymphoma, T-Cell
D008228	Lymphoma, Non-Hodgkin

ID	Term
D004317	Doxorubicin
D015122	Mercaptopurine
D008727	Methotrexate
D011241	Prednisone
D014747	Vinblastine
D014750	Vincristine