Bortezomib, Rituximab and Combination Chemotherapy in Tre... | NCT00477412

ID	Type	Description	Link
NCI-2018-01851	Registry Identifier	CTRP (Clinical Trial Reporting Program)
2006-0697	Other Identifier	M D Anderson Cancer Center

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety and the maximum tolerated dose (MTD) of bortezomib when added to the combination of rituximab, methotrexate, and cytarabine alternating with bortezomib, rituximab-hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone (hyperCVAD) in patients with untreated aggressive mantle cell lymphoma. (Phase I) II. Evaluate the time to failure (TTF) rate following therapy with bortezomib plus rituximab-hyperCVAD alternating with bortezomib plus rituximab-high dose methotrexate/cytarabine in patients between 18 and 79 years of age with untreated aggressive mantle cell lymphoma. (Phase II)

SECONDARY OBJECTIVES:

I. Evaluate overall response rate, complete remission rate, overall survival, and duration of remission. (Phase I) II. Evaluate overall response rate, overall survival, and duration of remission. (Phase II) III. Evaluate toxicity of the combination regimen. (Phase II) IV. Correlate outcome with pretreatment markers. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of bortezomib followed by a phase II study.

Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity.

Drug Combination I: Participants receive rituximab intravenously (IV) over 6 hours on day 1, cyclophosphamide IV over 3 hours twice daily (BID) on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone orally (PO) or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5.

Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.

After completion of study treatment, participants are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment (combination chemotherapy)	Experimental	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.	Drug: Bortezomib Drug: Cyclophosphamide Drug: Cytarabine Drug: Dexamethasone Drug: Doxorubicin Drug: Methotrexate Biological: Rituximab Drug: Vincristine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bortezomib	Drug	Given IV	Treatment (combination chemotherapy)	[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Tolerated Dose of Bortezomib (Phase I)	Determine the safety and the maximum tolerated dose (MTD) of bortezomib when added to the combination of rituximab, methotrexate, and cytarabine alternating with bortezomib, rituximab-hyperCVAD in patients with untreated aggressive mantle cell lymphoma.	Cycle 1 Day 1 - End of Cycle 2 up to 60 days.
Time to Failure (Phase II)	Failure will be defined as recurrence/progression of disease or death from either disease or toxicity. Bayesian toxicity monitoring schema will be used to monitor severe toxicity profile in combined therapy. Severe toxicity is defined as at least two episodes of neutropenic fever during treatment courses.	First date of diagnosis up to 5 years

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Overall Response Rate	Response rate is determined by CT scans of the chest, abdomen, and pelvis, unilateral BM biopsy and aspirate with lymphoma markers (if initially positive) and colonoscopy/endoscopy if applicable.	Up to 5 years
Overall Survival

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Confirmed diagnosis of previously untreated nodular or diffuse mantle cell lymphoma and their blastoid cytologic variant.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Serum bilirubin < 1.5 mg/dl and serum creatinine < 2.0 mg/dl within 14 days before enrollment (unless higher levels are due to lymphoma).
Platelet count > 100,000/mm^3 within 14 days before enrollment (unless due to lymphoma).
Absolute neutrophil count (ANC) > 1,000/mm^3 within 14 days before enrollment (unless due to lymphoma).
Cardiac ejection fraction >= 50% by echocardiogram (ECHO) or multigated acquisition (MUGA).
Patients must be willing to receive transfusions of blood products.
Voluntary written Institutional Review Board (IRB)-approved informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Female subject is either post-menopausal for at least 1 year before the Screening visit or surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of birth control, at the same time (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from the time of signing the informed consent through 30 days after the last dose of study treatment, or agree to completely abstain from heterosexual intercourse.
Male subject, even if surgically sterilized (ie, status post vasectomy) agrees to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study treatment, or agree to completely abstain from heterosexual intercourse.

Exclusion Criteria:

Human immunodeficiency virus (HIV) infection.
Central nervous system (CNS) involvement.
Co-morbid medical or psychiatric illnesses that preclude treatment with intense dose chemotherapy.
Concurrent or previous malignancy with < 90% probability of survival at 5 years.
Patient has >= grade 2 peripheral neuropathy within 14 days before enrollment.
Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiography (ECG) abnormality at screening has to be documented by the investigator as not medically relevant.
Patient has hypersensitivity to bortezomib, boron or mannitol.
Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
Participating in clinical trials with other investigational agents not included in this trial within 14 days of the start of this trial and throughout the duration of this trial.
Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.

Name	Affiliation	Role
Luhua (Michael) Wang	M.D. Anderson Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
M D Anderson Cancer Center		Houston	Texas	77030	United States

Label	URL
MD Anderson Cancer Center Website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Phase I Bortezomib 0.7 mg/m^2	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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	May 28, 2014

Arm/Group Information

ID	Title	Description
BG000	Phase I Bortezomib 0.7 mg/m^2	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
BG001	Phase I Bortezomib 1.0 mg/m^2	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
BG002	Phase 1 Maximum Tolerated Dose (MTD) 1.3 mg/m^2	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
BG003	Phase II- Treatment (Combination Chemotherapy)	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG0004 BG0013 BG0025 BG00395 BG004107

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

Maximum Tolerated Dose of Bortezomib (Phase I)

Determine the safety and the maximum tolerated dose (MTD) of bortezomib when added to the combination of rituximab, methotrexate, and cytarabine alternating with bortezomib, rituximab-hyperCVAD in patients with untreated aggressive mantle cell lymphoma.

Posted

Number

mg/m^2

Cycle 1 Day 1 - End of Cycle 2 up to 60 days.

ID	Title	Description
OG000	Phase 1 Maximum Tolerated Dose (MTD)	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.

Units	Counts
Participants	OG00012

Title

Denominators

Categories

Title	Measurements
	OG0001.3

Primary

Time to Failure (Phase II)

Failure will be defined as recurrence/progression of disease or death from either disease or toxicity. Bayesian toxicity monitoring schema will be used to monitor severe toxicity profile in combined therapy. Severe toxicity is defined as at least two episodes of neutropenic fever during treatment courses.

Posted

Median

Full Range

months

First date of diagnosis up to 5 years

ID	Title	Description
OG000	Phase II- Treatment (Combination Chemotherapy)	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.

Units	Counts
Participants

Secondary

Number of Participants With Overall Response Rate

Response rate is determined by CT scans of the chest, abdomen, and pelvis, unilateral BM biopsy and aspirate with lymphoma markers (if initially positive) and colonoscopy/endoscopy if applicable.

Overall Response Rate was measured in Phase II only. No data collected for Phase I.

Posted

Count of Participants

Participants

Up to 5 years

ID	Title	Description
OG000	Phase II- Treatment (Combination Chemotherapy)	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.

Units	Counts
Participants

Secondary

Overall Survival

Overall survival is the time in number of months from start of study treatment to date of death due to any cause.

Overall Response Rate was measured in Phase II only. No data collected for Phase I.

Posted

Median

Full Range

months

Date of diagnosis to last known date of survival, up to 5 years

ID	Title	Description
OG000	Phase II- Treatment (Combination Chemotherapy)	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.

Units	Counts
Participants

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	Phase I Bortezomib 0.7 mg/m^2	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.	4	4	1	4	4	4
EG001	Phase I Bortezomib 1.0 mg/m^2	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.	2	3	1	3	3	3
EG002	Phase 1 Maximum Tolerated Dose (MTD) Bortezomib 1.3 mg/m^2	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.	5	5	1	5	4	5
EG003	Phase II- Treatment (Combination Chemotherapy)	Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab IV over 6 hours on day 1, cyclophosphamide IV over 3 hours BID on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone PO or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.	7	94	45	94	94	94

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0004 affected4 at risk EG0013 affected3 at risk EG0024 affected5 at risk EG00394 affected94 at risk
Thrombocytopenia	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0004 affected4 at risk EG0013 affected3 at risk EG0024 affected5 at risk EG003
Infection	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected3 at risk EG0020 affected5 at risk EG003
Cellulitis	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected3 at risk EG0020 affected5 at risk EG003
Line Infection	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected3 at risk EG0020 affected5 at risk EG003
Syncope	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Mucositis	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected3 at risk EG0020 events0 affected5 at risk EG003
Atrial Fibrillation/ Flutter	Cardiac disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected3 at risk EG0021 affected5 at risk EG003
Fatigue	General disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected3 at risk EG0021 affected5 at risk EG003
Hypertension	Vascular disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected3 at risk EG0021 affected5 at risk EG003
Sinus Infection	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0021 affected5 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected3 at risk EG0021 affected5 at risk EG003
Nausea	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0021 affected5 at risk EG003
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected3 at risk EG0021 affected5 at risk EG003
Skin Rash	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Vomiting	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected3 at risk EG0020 affected5 at risk EG003
Leukocytosis	Investigations	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Anemia	Investigations	CTCAE (3.0)	Systematic Assessment	EG0004 affected4 at risk EG0013 affected3 at risk EG0024 affected5 at risk EG003
Cystitis	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0010 affected3 at risk EG0021 affected5 at risk EG003
Wound Infection	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Urinary Tract Infection	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected3 at risk EG0020 affected5 at risk EG003
Psychosis	Psychiatric disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Petechiae	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Peripheral Motor Neuropathy	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Leukopenia	Investigations	CTCAE (3.0)	Systematic Assessment	EG0003 affected4 at risk EG0013 affected3 at risk EG0021 affected5 at risk EG003
Hypotension	Vascular disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Hypokalemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Hypocalcemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected3 at risk EG0020 affected5 at risk EG003
Hypoalbuminemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected4 at risk EG0012 affected3 at risk EG0020 affected5 at risk EG003
Fever (Non-NP)	General disorders	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Elevated ALT	Investigations	CTCAE (3.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected3 at risk EG0021 affected5 at risk EG003
Elevated AST	Investigations	CTCAE (3.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected3 at risk EG0020 affected5 at risk EG003
Edema (HN)	General disorders	CTCAE (3.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected3 at risk EG0020 affected5 at risk EG003

Ancestor Terms

ID	Term
D001897	Boronic Acids
D000148	Acids, Noncarboxylic
D000143	Acids
D007287	Inorganic Chemicals
D001896	Boron Compounds
D009930	Organic Chemicals
D011719	Pyrazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D001087	Arabinonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated
D001557	Benzenesulfonates
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D001190	Arylsulfonates
D017739	Arylsulfonic Acids
D013451	Sulfonic Acids
D013456	Sulfur Acids
D013457	Sulfur Compounds
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D058846	Antibodies, Monoclonal, Murine-Derived
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
D014748	Vinca Alkaloids
D046948	Secologanin Tryptamine Alkaloids
D026121	Indole Alkaloids
D000470	Alkaloids
D007211	Indoles
D054836	Indolizidines
D007212	Indolizines

ID	Term
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
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

ID	Term
D000069286	Bortezomib
D003520	Cyclophosphamide
D003561	Cytarabine
D003907	Dexamethasone
D002123	Calcium Dobesilate
C059464	auricularum
C018038	dexamethasone acetate
C004180	dexamethasone 21-phosphate
D004317	Doxorubicin
D008727	Methotrexate
C015342	merphos
D000069283	Rituximab
C000626854	CT-P10
D014750	Vincristine