Combination Chemotherapy, Monoclonal Antibody, and Radiat... | NCT00068250

NCT00068250

ID	Type	Description	Link
CDR0000301563

Status Module

Sponsor/Collaborators Module

Name	Class
National Cancer Institute (NCI)	NIH
NRG Oncology	OTHER

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase I: Temozolomide 100 mg	Experimental	Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.	Drug: rituximab Drug: methotrexate Drug: temozolomide 100 mg/m^2 Radiation: radiation therapy Drug: post-radiation therapy temozolomide
Phase I: Temozolomide 150 mg	Experimental	Rituximab, methotrexate, temozolomide 150 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.	Drug: rituximab Drug: methotrexate Drug: temozolomide 150 mg/m^2 Radiation: radiation therapy Drug: post-radiation therapy temozolomide
Phase I: Temozolomide 200 mg	Experimental	Rituximab, methotrexate, temozolomide 200 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.	Drug: rituximab Drug: methotrexate Drug: temozolomide 200 mg/m^2 Radiation: radiation therapy Drug: post-radiation therapy temozolomide
Phase II: Temozolomide 100 mg	Experimental	Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.	Drug: rituximab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
rituximab	Drug	375 mg/m2, intravenously three days prior to the first cycle of methotrexate	Phase I: Temozolomide 100 mg Phase I: Temozolomide 150 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Phase I Participants Experiencing Toxicity	A dose limiting toxicity (DLT) is defined as any grade 3 or 4 non-hematological toxicity (other than grade 3 nausea/vomiting) or any hematological toxicity resulting in the discontinuation of temozolomide. Toxicity evaluation for this dose escalation includes all toxicities occurring prior to the start of radiation therapy. If the patient did not receive radiation therapy, then toxicity evaluation included all toxicities occurring through week 15. Any grade 5 toxicity would result in immediate suspension of accrual.	From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.
Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)	Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. (Please note that this outcome measure is considered the primary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )	Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.

Secondary Outcomes

Measure	Description	Time Frame
Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose)	Tumor response was centrally reviewed. Complete response: Disappearance of all enhancing tumor, the patient must be off steroid therapy and neurologically stable or improved; partial response: ≥ 50% decrease in enhancing tumor; progressive disease: ≥ 25% increase in a lesion, progressive or newly emergent meningeal or ocular disease. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Jon Glass, MD	Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Baptist Cancer Institute - Jacksonville		Jacksonville	Florida	32207	United States
Integrated Community Oncology Network at Southside Cancer Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27022122	Result	Glass J, Won M, Schultz CJ, Brat D, Bartlett NL, Suh JH, Werner-Wasik M, Fisher BJ, Liepman MK, Augspurger M, Bokstein F, Bovi JA, Solhjem MC, Mehta MP. Phase I and II Study of Induction Chemotherapy With Methotrexate, Rituximab, and Temozolomide, Followed By Whole-Brain Radiotherapy and Postirradiation Temozolomide for Primary CNS Lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016 May 10;34(14):1620-5. doi: 10.1200/JCO.2015.64.8634. Epub 2016 Mar 28.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Phase I: Temozolomide 100 mg	Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
FG001	Phase I: Temozolomide 150 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Drug: temozolomide 100 mg/m^2

Radiation: radiation therapy

Drug: post-radiation therapy temozolomide

Phase I: Temozolomide 200 mg

Phase II: Temozolomide 100 mg

Rituximab, methotrexate, temozolomide 150 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.

Eligible patients who started study treatment

Arm/Group Information

ID	Title	Description
BG000	Phase I: Temozolomide 100 mg	Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
BG001	Phase I: Temozolomide 150 mg	Rituximab, methotrexate, temozolomide 150 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
BG002	Phase II: Temozolomide 100 mg	Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
BG003	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, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	OG0001 OG0013

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001																		Other		Dose escalation followed the standard 3+3 design, although up to six patients could be accrued per dose level before suspending accrual for toxicity evaluation. If none of the first three patients (0/3), or one of the first three and none of the second three (1/3 and 0/3), experience a DLT, then the current dose level would be considered acceptable, and the next dose opened. Otherwise, the current dose level would be considered too toxic. The highest dose achieved with an acceptable level of toxicity was to considered the Maximum Tolerable Dose (MTD). If at any time a grade 5 toxicity was observed, accrual will be suspended, and the Study Chair would review the event. Furthermore, if the cumulative incidence (obtained by time to event analysis), at any time, of combined acute/late DLTs estimated the toxicity rate to be greater than 30% at any dose level, then the Executive Committee will be notified, and the committee would determine whether to stop accrual.

Primary

Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)

Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. (Please note that this outcome measure is considered the primary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )

Eligible patients on Temozolomide 100 mg arms who started study treatment

Posted

Number

95% Confidence Interval

percentage of participants

Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.

ID	Title	Description
OG000	Combined Temozolomide 100mg Arms	Phase I: Temozolomide 100mg and Phase II: Temozolomide 100 mg

Units	Counts
Participants	OG000

Secondary

Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose)

Tumor response was centrally reviewed. Complete response: Disappearance of all enhancing tumor, the patient must be off steroid therapy and neurologically stable or improved; partial response: ≥ 50% decrease in enhancing tumor; progressive disease: ≥ 25% increase in a lesion, progressive or newly emergent meningeal or ocular disease. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )

Eligible patients on Temozolomide 100 mg arms who started study treatment and have scans for central review

Posted

Count of Participants

Participants

From start of treatment to 10 weeks if RT received, to 15 weeks if not.

ID	Title	Description
OG000	Combined Temozolomide 100mg Arms	Phase I: Temozolomide 100mg and Phase II: Temozolomide 100 mg

Units	Counts
Participants	OG000

Secondary

Phase II: Progression-free Survival (Including Phase I Patients at Same Dose)

Progression is defined as greater than 25% increase in enhancing tumor or the appearance of new lesions in the brain, eye, or the appearance of a new positive cerebrospinal fluid (CSF) cytology. The patient may be neurologically stable or worse and on stable or increasing doses of corticosteroid. Progression-free survival time is defined as time from registration to the date of progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )

Eligible patients on Temozolomide 100 mg arms who started study treatment

Posted

Median

95% Confidence Interval

years

Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.

ID	Title	Description
OG000	Combined Temozolomide 100mg Arms	Phase I: Temozolomide 100mg and Phase II: Temozolomide 100 mg

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase I: Temozolomide 100 mg	Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.	3	6	6	6
EG001	Phase I: Temozolomide 150 mg	Rituximab, methotrexate, temozolomide 150 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.	4	6	6	6
EG002	Phase II: Temozolomide 100 mg	Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.	16	47	47	47

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Hemoglobin decreased	Blood and lymphatic system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Vomiting NOS	Gastrointestinal disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Fatigue	General disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Late RT Toxicity:Other NOS	General disorders	RTOG/EORTC Late Tox.	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Pain-other	General disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected47 at risk
Alanine aminotransferase increased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected47 at risk
Aspartate aminotransferase increased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected47 at risk
Leukopenia NOS	Investigations	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0025 affected47 at risk
Neutropenia	Investigations	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0012 affected6 at risk EG0025 affected47 at risk
Platelet count decreased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0027 affected47 at risk
Alkalosis NOS	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Hyperglycemia NOS	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected47 at risk
Ataxia NEC	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Convulsions NOS	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected47 at risk
Encephalopathy NOS	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Headache NOS	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Learning disorder NOS	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Peripheral motor neuropathy	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Speech disorder NEC	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected47 at risk
Renal failure NOS	Renal and urinary disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected47 at risk
Thrombosis NOS	Vascular disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hematologic-Other	Blood and lymphatic system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0022 affected47 at risk
Hemoglobin decreased	Blood and lymphatic system disorders	CTC (2.0)	Non-systematic Assessment	EG0005 affected6 at risk EG0016 affected6 at risk EG00239 affected47 at risk
Hemolysis NOS	Blood and lymphatic system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected47 at risk
Platelet transfusion	Blood and lymphatic system disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0023 affected47 at risk
Arrhythmia NOS	Cardiac disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0022 affected47 at risk
Edema NOS	Cardiac disorders	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0012 affected6 at risk EG00212 affected47 at risk
Cushingoid	Endocrine disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Cataract NEC	Eye disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Diplopia	Eye disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0025 affected47 at risk
Dry eye NEC	Eye disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0023 affected47 at risk
Late RT Toxicity:Eye NOS	Eye disorders	RTOG/EORTC Late Tox.	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0025 affected47 at risk
Ocular-Other	Eye disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0025 affected47 at risk
Vision blurred	Eye disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG00215 affected47 at risk
Constipation	Gastrointestinal disorders	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0011 affected6 at risk EG00211 affected47 at risk
Diarrhea NOS	Gastrointestinal disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG00211 affected47 at risk
Esophageal spasm	Gastrointestinal disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected47 at risk
Esophagitis NOS	Gastrointestinal disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0027 affected47 at risk
Nausea	Gastrointestinal disorders	CTC (2.0)	Non-systematic Assessment	EG0005 affected6 at risk EG0014 affected6 at risk EG00232 affected47 at risk
Stomatitis	Gastrointestinal disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG00211 affected47 at risk
Vomiting NOS	Gastrointestinal disorders	CTC (2.0)	Non-systematic Assessment	EG0005 affected6 at risk EG0011 affected6 at risk EG00225 affected47 at risk
Fatigue	General disorders	CTC (2.0)	Non-systematic Assessment	EG0006 affected6 at risk EG0016 affected6 at risk EG00242 affected47 at risk
Late RT Toxicity:Other NOS	General disorders	RTOG/EORTC Late Tox.	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG00210 affected47 at risk
Pain-other	General disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG00216 affected47 at risk
Rigors	General disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0025 affected47 at risk
Hepatic-Other	Hepatobiliary disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0022 affected47 at risk
Allergy-Other	Immune system disorders	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0010 affected6 at risk EG0020 affected47 at risk
Infection NOS	Infections and infestations	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0029 affected47 at risk
Infection with grade 3 or 4 neutropenia	Infections and infestations	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0025 affected47 at risk
Dermatitis radiation NOS	Injury, poisoning and procedural complications	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0013 affected6 at risk EG00217 affected47 at risk
Ecchymosis	Injury, poisoning and procedural complications	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0025 affected47 at risk
Late RT Toxicity:Skin(within RT field)NOS	Injury, poisoning and procedural complications	RTOG/EORTC Late Tox.	Systematic Assessment	EG0003 affected6 at risk EG0010 affected6 at risk EG0029 affected47 at risk
Operative injury of vein/artery	Injury, poisoning and procedural complications	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected47 at risk
Alanine aminotransferase increased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0005 affected6 at risk EG0013 affected6 at risk EG00227 affected47 at risk
Aspartate aminotransferase increased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0004 affected6 at risk EG0012 affected6 at risk EG00224 affected47 at risk
Blood alkaline phosphatase NOS increased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0026 affected47 at risk
Blood bilirubin increased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0026 affected47 at risk
Blood creatinine increased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0011 affected6 at risk EG00215 affected47 at risk
Gamma-glutamyltransferase increased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0021 affected47 at risk
Leukopenia NOS	Investigations	CTC (2.0)	Non-systematic Assessment	EG0004 affected6 at risk EG0015 affected6 at risk EG00226 affected47 at risk
Lymphopenia	Investigations	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG00220 affected47 at risk
Metabolic-Other	Investigations	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0025 affected47 at risk
Neutropenia	Investigations	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG00219 affected47 at risk
Platelet count decreased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0004 affected6 at risk EG0011 affected6 at risk EG00230 affected47 at risk
Prothrombin time prolonged	Investigations	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0022 affected47 at risk
Weight decreased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG00210 affected47 at risk
Weight increased	Investigations	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0026 affected47 at risk
Anorexia	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0013 affected6 at risk EG00217 affected47 at risk
Blood albumin decreased	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0025 affected47 at risk
Blood bicarbonate decreased	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected47 at risk
Blood magnesium decreased	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0021 affected47 at risk
Dehydration	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0025 affected47 at risk
Hyperglycemia NOS	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0012 affected6 at risk EG00212 affected47 at risk
Hyperkalemia	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0025 affected47 at risk
Hypernatremia	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0024 affected47 at risk
Hyperuricemia	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected47 at risk
Hypocalcemia	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0005 affected6 at risk EG0014 affected6 at risk EG00226 affected47 at risk
Hypoglycaemia NOS	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0024 affected47 at risk
Hypokalemia	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG00214 affected47 at risk
Hyponatremia	Metabolism and nutrition disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0028 affected47 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0026 affected47 at risk
Bone pain	Musculoskeletal and connective tissue disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected47 at risk
Joint, muscle, or bone-Other	Musculoskeletal and connective tissue disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0023 affected47 at risk
Muscle weakness NOS	Musculoskeletal and connective tissue disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG00210 affected47 at risk
Amnesia NEC	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0012 affected6 at risk EG00214 affected47 at risk
Ataxia NEC	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0012 affected6 at risk EG00213 affected47 at risk
Cerebral ischaemia	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected47 at risk
Convulsions NOS	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0025 affected47 at risk
Dizziness (exc vertigo)	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0027 affected47 at risk
Headache NOS	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0004 affected6 at risk EG0012 affected6 at risk EG00230 affected47 at risk
Late RT Toxicity:Brain NOS	Nervous system disorders	RTOG/EORTC Late Tox.	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0025 affected47 at risk
Late RT Toxicity:Encephalopathy NOS	Nervous system disorders	RTOG/EORTC Late Tox.	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0022 affected47 at risk
Neuralgia NOS	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0027 affected47 at risk
Neurologic-Other	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0023 affected47 at risk
Peripheral motor neuropathy	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0013 affected6 at risk EG00215 affected47 at risk
Peripheral sensory neuropathy	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0012 affected6 at risk EG00210 affected47 at risk
Speech disorder NEC	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0010 affected6 at risk EG0026 affected47 at risk
Taste disturbance	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0010 affected6 at risk EG00214 affected47 at risk
Tremor NEC	Nervous system disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected47 at risk
Anxiety NEC	Psychiatric disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0029 affected47 at risk
Confusion	Psychiatric disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0029 affected47 at risk
Depression NEC	Psychiatric disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0012 affected6 at risk EG0029 affected47 at risk
Insomnia NEC	Psychiatric disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG00210 affected47 at risk
Renal/GU-Other	Renal and urinary disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0021 affected47 at risk
Urinary incontinence	Renal and urinary disorders	CTC (2.0)	Non-systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0025 affected47 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0026 affected47 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected47 at risk
Alopecia	Skin and subcutaneous tissue disorders	CTC (2.0)	Non-systematic Assessment	EG0004 affected6 at risk EG0012 affected6 at risk EG00224 affected47 at risk
Dermatitis exfoliative NOS	Skin and subcutaneous tissue disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG00211 affected47 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected47 at risk
Petechiae	Skin and subcutaneous tissue disorders	CTC (2.0)	Non-systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected47 at risk
Pruritus NOS	Skin and subcutaneous tissue disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0020 affected47 at risk
Skin-Other	Skin and subcutaneous tissue disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0022 affected47 at risk
Hypertension NOS	Vascular disorders	CTC (2.0)	Non-systematic Assessment	EG0003 affected6 at risk EG0010 affected6 at risk EG0026 affected47 at risk
Thrombosis NOS	Vascular disorders	CTC (2.0)	Non-systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0025 affected47 at risk

The 200 mg/m^2 treatment arm in the phase I component of the study did not open. Outcome measures are categorized as the phase I or phase II study component, but phase I patients at corresponding dose level are included in the phase II analyses.

Certain Agreements

ID	Term
D016543	Central Nervous System Neoplasms
D008223	Lymphoma

Ancestor Terms

ID	Term
D009423	Nervous System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D009422	Nervous System Diseases
D009370	Neoplasms by Histologic Type
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D000069283	Rituximab
D008727	Methotrexate
D000077204	Temozolomide
D011878	Radiotherapy

Ancestor Terms

ID	Term
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
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003606	Dacarbazine
D014226	Triazenes
D009930	Organic Chemicals
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D013812	Therapeutics