Trial Outcomes & Findings for A Study of ONTAK and CHOP in Newly Diagnosed, Peripheral T-Cell Lymphoma (NCT NCT00211185)

NCT ID: NCT00211185

Last Updated: 2020-03-18

Results Overview

An adverse event (AE) was any medical occurrence in a participant who was administered denileukin diftitox and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and did not necessarily have a causal relationship with this treatment. An AE included any side effect, injury, toxicity, sensitivity reaction, or any undesirable clinical or laboratory event that was not normally observed in the participant. Safety was assessed for all participants who received at least one dose of study medication and was monitored throughout the study. Safety evaluations were based on the incidence, intensity, and type of AE, and clinically significant changes in the participant's medical history, physical examination findings, vital signs, and clinical laboratory results. Participants also notified the study staff of any problems that occurred between visits by telephone, and if necessary, were evaluated by the investigator or study staff at an unscheduled interim visit.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 49 participants
• Primary outcome timeframe: From date of first dose up to approximately 4 weeks after discontinuation of denileukin diftitox and CHOP, or after early withdrawal for any reason, up to approximately 5 years 9 months
• Results posted on: 2020-03-18

Participant Flow

Participant milestones

Measure	Denileukin Diftitox in Combination With CHOP Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Overall Study STARTED	49
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Measure	Denileukin Diftitox in Combination With CHOP Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Overall Study Death	2
Overall Study Disease progression	7
Overall Study Withdrawal by Subject	6
Overall Study Physician Decision	5

Baseline Characteristics

A Study of ONTAK and CHOP in Newly Diagnosed, Peripheral T-Cell Lymphoma

Baseline characteristics by cohort

Measure	Denileukin Diftitox in Combination With CHOP n=49 Participants Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Age, Continuous	53.7 Years STANDARD_DEVIATION 13.2 • n=93 Participants
Sex: Female, Male Female	26 Participants n=93 Participants
Sex: Female, Male Male	23 Participants n=93 Participants

PRIMARY outcome

Timeframe: From date of first dose up to approximately 4 weeks after discontinuation of denileukin diftitox and CHOP, or after early withdrawal for any reason, up to approximately 5 years 9 months

Population: The Safety Population was used and defined as all treated participants. Participants who did not receive at least one dose of study medication were excluded from this population. For this study, the safety population is the same as the Intent to Treat (ITT) population.

An adverse event (AE) was any medical occurrence in a participant who was administered denileukin diftitox and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and did not necessarily have a causal relationship with this treatment. An AE included any side effect, injury, toxicity, sensitivity reaction, or any undesirable clinical or laboratory event that was not normally observed in the participant. Safety was assessed for all participants who received at least one dose of study medication and was monitored throughout the study. Safety evaluations were based on the incidence, intensity, and type of AE, and clinically significant changes in the participant's medical history, physical examination findings, vital signs, and clinical laboratory results. Participants also notified the study staff of any problems that occurred between visits by telephone, and if necessary, were evaluated by the investigator or study staff at an unscheduled interim visit.

Outcome measures

Measure	Denileukin Diftitox in Combination With CHOP n=49 Participants Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Fatigue	63.3 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Nausea	46.9 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Hemoglobin	40.8 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Neuropathy-sensory	40.8 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Alanine transaminase	34.7 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Hyperglycemia	34.7 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Hypoalbuminemia	34.7 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Leukocytes	34.7 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Fever	32.7 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Hypocalcemia	30.6 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Lymphopenia	30.6 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Aspartate transaminase	28.6 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Dyspnea	28.6 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Platelets	28.6 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Alopecia	26.5 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Neutrophils	26.5 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Constipation	24.5 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Edema-limb	20.4 Percentage of participants
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants Hyponatremia	20.4 Percentage of participants

PRIMARY outcome

Timeframe: From date of first dose up to approximately 4 weeks after discontinuation of denileukin diftitox and CHOP, or after early withdrawal for any reason, up to approximately 5 years 9 months

Population: Safety population

A treatment-related adverse event was any medical occurrence in a participant who was administered denileukin diftitox and CHOP and was determined to be possibly, probably, or definitely related to study treatment. An AE included any side effect, injury, toxicity, sensitivity reaction, or any undesirable clinical or laboratory event that was not normally observed in the participant. Safety was assessed for all participants who received at least one dose of study medication and was monitored throughout the study. Safety evaluations were based on the incidence, intensity, and type of AE, and clinically significant changes in the participant's medical history, physical examination findings, vital signs, and clinical laboratory results. Participants also notified the study staff of any problems that occurred between visits by telephone, and if necessary, were evaluated by the investigator or study staff at an unscheduled interim visit.

Outcome measures

Measure	Denileukin Diftitox in Combination With CHOP n=49 Participants Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Fatigue	55.1 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Nausea	36.7 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Hemoglobin	30.6 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Leukocytes	30.6 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Lymphopenia	30.6 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Dyspnea	26.5 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Neuropathy-sensory	26.5 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Alanine transaminase	24.5 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Alopecia	22.4 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Platelets	22.4 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Neutrophils	20.4 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Constipation	18.4 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Hypoalbuminemia	18.4 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Aspartate transaminase	16.3 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Edema-limb	16.3 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Fever	16.3 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Hypocalcemia	16.3 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Allergic reaction	12.2 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Anorexia	12.2 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Taste alteration	12.2 Percentage of participants
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants Febrile neutropenia	10.2 Percentage of participants

PRIMARY outcome

Timeframe: From date of first dose up to approximately 4 weeks after discontinuation of denileukin diftitox and CHOP, or after early withdrawal for any reason, up to approximately 5 years 9 months

Population: Safety population

Treatment-related AEs were medical occurrences determined to be possibly, probably, or definitely related to study treatment. Severity grading of the AE was according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) severity scale (grades 1 - 5) with grade 3 representing a severe AE. Safety was assessed for all participants who received at least one dose of study medication and was monitored throughout the study. Safety evaluations were based on the incidence, intensity, and type of AE, and clinically significant changes in the participant's medical history, physical examination findings, vital signs, and clinical laboratory results. Participants also notified the study staff of any problems that occurred between visits by telephone, and if necessary, were evaluated by the investigator or study staff at an unscheduled interim visit.

Outcome measures

Measure	Denileukin Diftitox in Combination With CHOP n=49 Participants Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Vascular: Thrombosis/embolism	4.1 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Allergy/Immunology: Allergic reaction	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Blood/Bone Marrow: Hemoglobin	8.2 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Blood/Bone Marrow: Leukocytes	16.3 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Blood/Bone Marrow: Lymphopenia	24.5 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Blood/Bone Marrow: Neutrophils	16.3 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Blood/Bone Marrow: Platelets	12.2 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Cardiac Arrhythmia: Supra Arrhyth:Sinus Tachy	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Cardiac General: Cardiac ischemia/infarction	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Cardiac General: Cardiopulmonary arrest	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Coagulation: Coagulation-other	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Constitutional symptoms: Fatigue	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Constitutional symptoms: Fever	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Death: Death, NOS	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Infection: Febrile neutropenia	10.2 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Infection: Inf, 3-4 ANC: cath-related	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Infection: Infection-other	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Infection: Lung Inf, 0-2 ANC: lung	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Metabolic/Laboratory: Alanine transaminase (ALT)	4.1 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Metabolic/Laboratory: Aspartate transaminase (AST)	4.1 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Metabolic/Laboratory: CPK	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Metabolic/Laboratory: Cholesterol	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Metabolic/Laboratory: GGT	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Metabolic/Laboratory: Hypoalbuminemia	4.1 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Metabolic/Laboratory: Hypokalemia	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Pain: Pain-other	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Pulmonary/Upper Respiratory: Dyspnea	4.1 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Pulmonary/Upper Respiratory: Hypoxia	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Pulmonary/Upper Respiratory: Pneumonitis	2.0 Percentage of participants
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class Syndromes: Tumor Lysis syndrome	2.0 Percentage of participants

PRIMARY outcome

Timeframe: From date of first dose up to approximately 4 weeks after discontinuation of denileukin diftitox and CHOP, or after early withdrawal for any reason, up to approximately 5 years 9 months

Population: Safety population

A serious adverse event (SAE) was any AE that occurred at any dose and resulted in any of the following outcomes: death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that did not result in death, were life-threatening, or required hospitalization were considered a SAE when based upon appropriate medical judgment, jeopardized the participant and required medical or surgical intervention to prevent one of the outcomes listed above. Possibly Related (Poss Rel) applied to AEs judged to be perhaps related to study medication, Probably Related (Prob Rel) applied to AEs judged to have a high degree of certainty as related to study medication, and Definitely Related (Def Rel) related applied to AEs that were judged to be without a doubt related to study medication.

Outcome measures

Measure	Denileukin Diftitox in Combination With CHOP n=49 Participants Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Tumor lysis syndrome (grade 5) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Febrile neutropenia (grade 3) Prob Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Febrile neutropenia (grade 3) Poss Rel	4 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Fever (grade 3) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Fever (grade 2) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Thrombosis/embolism (grade 3) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Neutrophils (grade 3) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Neutrophils (grade 4) Poss Rel	3 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Left vent. diastolic dysfunct. (grade 1) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Allergic reaction (grade 4) Def Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Platelets (grade 4) Prob Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Platelets (grade 4) Poss Rel	2 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Dyspnea (grade 3) Prob Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Pneumonitis (grade 3) Prob Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Lung Inf, 0-2 ANC: lung (grade 3) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Leukocytes (grade 4) Poss Rel	2 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Leukocytes (grade 4) Prob Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Lymphopenia (grade 4) Poss Rel	2 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Inf, 3-4 ANC: cath-related (grade 3) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Allergy-other (grade 1) Def Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Infection-other (grade 3) Poss Rrel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Cardiac ischemia (grade 5) Def Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Cardiopulmonary arrest (grade 4) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Supra Arrhyth: Sinus Tachy. (grade 4) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Death, NOS (grade 5) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Edema-limb (grade 1) Poss Rel	1 Participants
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events Pain-other (grade 3) Poss Rel	1 Participants

SECONDARY outcome

Timeframe: From the start of the treatment to the date of participant's death assessed up to 5 years 9 months

Population: Intent to treat (ITT) population included all participants who signed an informed consent and were deemed eligible to participate by the investigator based on the screening assessments, and started at least 1 cycle of study treatment. It is the same as the Safety Population (SP) for this study.

Response rate was defined as the percentage of the ITT population who achieved a Complete Response (CR), Unconfirmed Complete Response (CRu), or Partial Response (PR). The International Working Group recommendations on non-Hodgkin's lymphoma response criteria were used to determine response to therapy. Largely, the protocol defined the response criteria as: 1) CR, loss of all detectable clinical and radiographic evidence of disease and disease-related symptoms if present before therapy; 2) CRu, CR with the caveats, response to therapy was accompanied with a 75% reduction in measurable lesion size and/or an indeterminate bone marrow biopsy (if initially positive); and 3) PR, less than or equal to 50% decrease in the sum of the measurements of tumor diameters, no increase in the size of other nodes, liver, or spleen, hepatic or spleen nodules regressed by at least 50%, and/or no new sites of disease.

Outcome measures

Measure	Denileukin Diftitox in Combination With CHOP n=49 Participants Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Overall Response in the Intent To Treat (ITT) Population Inadequate assessment	20.4 Percentage of participants
Overall Response in the Intent To Treat (ITT) Population Confirmed complete response	51.0 Percentage of participants
Overall Response in the Intent To Treat (ITT) Population Unconfirmed complete response	4.1 Percentage of participants
Overall Response in the Intent To Treat (ITT) Population Partial response	10.2 Percentage of participants
Overall Response in the Intent To Treat (ITT) Population Stable disease	6.1 Percentage of participants
Overall Response in the Intent To Treat (ITT) Population Disease progression	4.1 Percentage of participants
Overall Response in the Intent To Treat (ITT) Population Early death	4.1 Percentage of participants

SECONDARY outcome

Timeframe: From the start of the treatment to the date of the participant's death assessed up to 5 years 9 months

Population: EA population includes all participants who received at least 2 cycles of study drug treatment, were eligible to participate or ineligible with an exception granted by the principal investigator (PI), had bidimensional lesions at baseline, and had at least 1 disease response assessment form submitted following cycle 2.

Response rate was defined as the percentage of the EA population who achieved a CR, CRu, or PR. The International Working Group recommendations on non-Hodgkin's lymphoma response criteria were used to determine response to therapy. Largely, the protocol defined the response criteria as: 1) CR, loss of all detectable clinical and radiographic evidence of disease and disease-related symptoms if present before therapy; 2) CRu, CR with the caveats, response to therapy was accompanied with a 75% reduction in measurable lesion size and/or an indeterminate bone marrow biopsy (if initially positive); and 3) PR, less than or equal to 50% decrease in the sum of the measurements of tumor diameters, no increase in the size of other nodes, liver, or spleen, hepatic or spleen nodules regressed by at least 50%, and/or no new sites of disease.

Outcome measures

Measure	Denileukin Diftitox in Combination With CHOP n=37 Participants Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Overall Response in the Efficacy Analyzable (EA) Population Confirmed complete response	67.6 Percentage of participants
Overall Response in the Efficacy Analyzable (EA) Population Unconfirmed complete response	5.4 Percentage of participants
Overall Response in the Efficacy Analyzable (EA) Population Partial response	13.5 Percentage of participants
Overall Response in the Efficacy Analyzable (EA) Population Stable disease	8.1 Percentage of participants
Overall Response in the Efficacy Analyzable (EA) Population Disease progression	5.4 Percentage of participants
Overall Response in the Efficacy Analyzable (EA) Population Early death	0.0 Percentage of participants
Overall Response in the Efficacy Analyzable (EA) Population Inadequate assessment	0.0 Percentage of participants

SECONDARY outcome

Timeframe: From the date of the first documented CR (confirmed or unconfirmed) or PR until the date of first documentation of recurrent or PD or death, assessed up to 5 years 9 months

Population: EA population

Duration of response was defined as the length of time from the first date at which the response criteria were met (taking the earliest date at which a PR, CRu, or the confirmed CR occurred) until the date that recurrent or PD or death was accurately documented, per the criteria defined for progression-free survival (PFS). All participants within the EA population who achieved a response per the criteria defined were included in the duration of the response analysis. Participants lost to follow-up prior to PD or death were censored at the date they were last known to still be responding to treatment. Duration of response was estimated using the Kaplan-Meier method with the median duration of response summarized.

Outcome measures

Measure

Denileukin Diftitox in Combination With CHOP n=32 Participants Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.

Duration of Response

29.7 Months Standard Deviation NA 90% confidence interval could not be calculated because high number of participants were censored from the analysis.

SECONDARY outcome

Timeframe: From the date of first dose of study drug until date of first documentation of PD, recurrence, or death from any cause, assessed up to 5 years 9 months

Population: ITT population

PFS was defined as the period of time from treatment start to the first documentation of PD, recurrence, or death. PD was defined as a greater than or equal to 50% increase from baseline in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or non-responders, or the appearance of any new lesions during or at the end of therapy. PFS was censored at the last date for which the response assessment resulted in the absence of PD for participants who did not demonstrate objective progression or recurrence. Participants who withdrew prior to evidence of disease progression or recurrence, PFS was censored at the last date assessment showed an absence of PD.

Outcome measures

Measure

Denileukin Diftitox in Combination With CHOP n=49 Participants Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.

Progression-Free Survival

12.4 Weeks Standard Deviation 6.1

SECONDARY outcome

Timeframe: From date of randomization until death, or administrative close of study, whichever came first, assessed up to 5 years 9 months

Population: ITT population

Overall Survival (OS) was defined as the time from the date of registration to the date of the participant's death. OS was determined by reviewing all participant's records every 6 months until the study was administratively closed or all participants died, whichever occurred first. Participants who were lost to follow-up but were still alive at the date of last contact were censored at the date of last contact. Participants who did not have a recorded date of death were censored for OS at the last date at which they were known to be alive.

Outcome measures

Measure

Denileukin Diftitox in Combination With CHOP n=49 Participants Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.

Percentage of Participants With Overall Survival

63.3 Percentage of participants

Adverse Events

Denileukin Diftitox in Combination With CHOP

Serious events: 25 serious events

Other events: 49 other events

Deaths: 18 deaths

Serious adverse events

Measure	Denileukin Diftitox in Combination With CHOP n=49 participants at risk Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Immune system disorders Allergic reaction	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Immune system disorders Allergy-other	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Blood and lymphatic system disorders Leukocytes	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Blood and lymphatic system disorders Lymphopenia	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Blood and lymphatic system disorders Neutrophils	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Blood and lymphatic system disorders Platelets	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Supra Arrhyth: Sinus Tachy	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Cardiac ischemia/infarction	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Cardiopulmonary arrest	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Hypotension	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Left vent. diastolic dysfunct.	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Fever	12.2% 6/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Death NOS	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Disease progression, NOS	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders GI obstruction, small bowel	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Lung hemorrhage, lung	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Febrile Neutropenia	12.2% 6/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Inf. 0-2 ANC: cath-related	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Inf, 3-4 ANC: blood	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Inf, 3-4 ANC: cath-related	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Infection-other	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Lung inf, 0-2 ANC: lung	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Skin Inf, 0-2 ANC: skin	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Edema-limb	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Alanine transaminase (AST)	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Creatinine phosphokinase (CPK)	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Cerebral spinal fluid (CSF) leak	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Eye disorders Neurop. lat dev. of eye	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Cardio. pain cardiac/heart	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders GI pain, abdomen	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Pain-other	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Pain NOS	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Pneumonitis	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Renal and urinary disorders Renal failure	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Tumor lysis syndrome	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Vascular disorders Thrombosis/embolism	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.

Other adverse events

Measure	Denileukin Diftitox in Combination With CHOP n=49 participants at risk Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
Blood and lymphatic system disorders Edema-limb	18.4% 9/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations ALT	34.7% 17/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Fatigue	63.3% 31/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Weight gain	10.2% 5/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hypocalcemia	28.6% 14/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Skin and subcutaneous tissue disorders Dry skin	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Fever	22.4% 11/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hypoalbuminemia	34.7% 17/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Skin and subcutaneous tissue disorders Ulceration	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations AST	28.6% 14/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Rigors/chills	14.3% 7/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Dyspnea	28.6% 14/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Blood and lymphatic system disorders Lymphopenia	30.6% 15/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Constipation	24.5% 12/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hemoglobin	40.8% 20/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Nausea	46.9% 23/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Leukocytes	34.7% 17/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Neutrophils	26.5% 13/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Cough	16.3% 8/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Diarrhea	14.3% 7/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Musculoskeletal-other	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Nervous system disorders Neuropathy-motor	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Renal and urinary disorders Incontinence, urinary	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Neuro Inf, 0-2 ANC: periph nrv	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Alopecia	26.5% 13/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Skin and subcutaneous tissue disorders Rash	12.2% 6/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Alkaline phosphatase	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Sweating	12.2% 6/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Weight loss	10.2% 5/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Mucositis, funct: oral cav	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Proteinuria	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hypokalemia	12.2% 6/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Muscle weakness: up. extrem.	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Musculo. pain: bone	16.3% 8/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Platelets	28.6% 14/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hyperglycemia	32.7% 16/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hemoglobinuria	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Nail changes	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Reproductive system and breast disorders Libido	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Taste alteration	18.4% 9/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Nervous system disorders Neuro Pain: head/headache	14.3% 7/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Reproductive system and breast disorders Vaginitis	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Skin and subcutaneous tissue disorders Pruritus	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Vascular disorders Thrombosis/embolism	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Immune system disorders Allergic reaction	12.2% 6/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Palpitations	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Heartburn	16.3% 8/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Hot flashes	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Eye disorders Blurred vision	10.2% 5/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Flatulence	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Psychiatric disorders Confusion	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Cardio. Pain: cardiac/heart	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Left vent. diastolic function	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Psychiatric disorders Mood alterations: depression	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Skin Inf., 0-2 ANC: skin	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hyperkalemia	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Arthritis	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Nervous system disorders Neurop: hear & bal.	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hyponatremia	20.4% 10/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hyperuricemia	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Blood and lymphatic system disorders Edema-trunk/genital	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Musculo. Pain: joint	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Lung Pain: chest/thorax	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Musculo. Pain: limb	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Blood and lymphatic system disorders Edema-Head and Neck	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Eye disorders Eye Infection Unk ANC: conjuct.	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Lung Pain: throat/phar/lar	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Nervous system disorders Dizziness	10.2% 5/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Hypotension	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
General disorders Insomnia	10.2% 5/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Mucositis, clin: oral cavity	12.2% 6/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Airway obstruction: trachea	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Eye disorders Watery eye	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Bicarbonate, serum low	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Immune system disorders Rhinitis	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Hemorrhoids	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders GI Pain: anus	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Nervous system disorders Memory impairment	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Vomiting	16.3% 8/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Nervous system disorders Tremor	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Dry mouth	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Blood and lymphatic system disorders Blood-other	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Nervous system disorders Neuro Pain: neuralg/periph nrv	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Anorexia	14.3% 7/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hypomagnesemia	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Eye disorders Eye inf, 0-2 ANC: conjunct.	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Dehydration	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders GI Pain: abdomen	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Eye disorders Diplopia	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders GI Inf, 0-2 ANC: stomach	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Nasal/Paranasal reactions	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Dysphagia	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Musculo. Pain: back	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Bilirubin	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Muscle weakness: whole body	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Hepatobiliary disorders Liver dysfunction	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations Skin Inf, 0-2 ANC: lip/perior	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Supra Arrhyth: supra tachy	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders GI-other	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Musculo. Pain: muscle	12.2% 6/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Creatinine	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Bronchospasm	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hypernatremia	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Metabolic/Lab-other	8.2% 4/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations PTT	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Coagulation-other	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Musculo Pain: neck	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Pericardial effusion	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Skin and subcutaneous tissue disorders Dermatology-other	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Salivary gland changes	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Vascular disorders Acute vascular leak syndrome	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Nervous system disorders Neuropathy-sensory	40.8% 20/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Skin and subcutaneous tissue disorders Hyperpigmentation	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Respiratory, thoracic and mediastinal disorders Lung Pain: chest wall	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations cTnI	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Cardiac disorders Cardiac-general-other	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations INR	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Acidosis	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Hypoglycemia	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders Mucositis, clin: esophagus	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Nervous system disorders Mood alteration: anxiety	6.1% 3/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Infections and infestations GI Inf, 0-2 ANC: gums	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations CPK	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Muscle weakness: low extrem	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations Cholesterol	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Musculoskeletal and connective tissue disorders Gait/Walking	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders GI hemorrhage: lower GI	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Gastrointestinal disorders GI Inf, 0-2 ANC: abdomen NOS	2.0% 1/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
Investigations GGT	4.1% 2/49 • From date of administration of first dose up to 30 days after the last dose, or for any event that was present prior to study drug and continued after the first dose of study treatment but worsened in intensity, up to approximately 5 years 9 months Treatment-emergent adverse events and serious adverse events were reported. Safety population included all treated participants. Participants who did not receive at least 1 dose of study treatment were excluded from this population. All toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 1-888-274-2378

Email: esi_oncmedinfo@eisai.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER