Trial Outcomes & Findings for Iodine-131 Anti-B1 Antibody (Tositumomab and Iodine I 131 Tositumomab) for Previously Untreated, Advanced-stage, Low Grade Non-Hodgkin's Lymphoma (NCT NCT00996996)

Last Updated: 2017-01-11

Results Overview

Confirmed response required CR, CCR, or PR, which were confirmed by 2 separate response evaluations \>=4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

77 participants

Primary outcome timeframe

From Study Day 0 (start of treatment) up to 12 years (long-term follow up)

Results posted on

2017-01-11

Participant Flow

Participant milestones

Participant milestones
Measure	Tositumomab and Iodine I-131 Tositumomab Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Overall Study STARTED	77
Overall Study COMPLETED	44
Overall Study NOT COMPLETED	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Tositumomab and Iodine I-131 Tositumomab Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Overall Study Progressive Disease	10
Overall Study Non-compliance	8
Overall Study Lost to Follow-up	9
Overall Study Death	5
Overall Study Did Not Receive Study Medications	1

Baseline Characteristics

Iodine-131 Anti-B1 Antibody (Tositumomab and Iodine I 131 Tositumomab) for Previously Untreated, Advanced-stage, Low Grade Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Age, Continuous	48.1 Years STANDARD_DEVIATION 9.9 • n=5 Participants
Gender Female	35 Participants n=5 Participants
Gender Male	41 Participants n=5 Participants
Race/Ethnicity, Customized White	74 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants

PRIMARY outcome

Timeframe: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)

Population: ITT-Exposed Population: all participants who were enrolled in the study and received at least one dose of study drug. Only participants evaluable for confirmed response were assessed.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=75 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants With Confirmed Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR)	72 participants

PRIMARY outcome

Timeframe: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)

Population: ITT-Exposed Population

CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants With Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), or Partial Response (PR)	74 participants

PRIMARY outcome

Timeframe: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)

Population: ITT-Exposed Population. Only participants evaluable for confirmed response (R) were assessed. R had to be confirmed by a consecutive R that was the same or better \>=4 weeks apart. Each individual confirmed R category only counts the R confirmed by the exact same R; therefore, not all possible combinations are represented in the table.

Responses were confirmed by two separate response evaluations at least 4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=75 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) CR	53 participants
Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) CCR	2 participants
Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) CR+CCR	57 participants
Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) PR	13 participants

PRIMARY outcome

Timeframe: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)

Population: ITT-Exposed Population

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) CR	56 participants
Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) CCR	3 participants
Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) CR+CCR	59 participants
Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) PR	15 participants

SECONDARY outcome

Timeframe: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)

Population: ITT-Exposed Population. Only participants who experienced confirmed CR, CCR, or PR with PD were assessed. Response (R) had to be confirmed by a consecutive R that was the same or better \>=4 weeks apart. Each individual confirmed R category only counts the R confirmed by the exact same R; therefore, not all possible combinations are represented.

Duration of response (CR, CCR, or PR) is defined as the time from the first documented response to the first documented progression. Progressive Disease (PD) is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=45 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
The Estimated Value Represents the Percentage of Participants With a PR Confirmed CR+CCR+PR, n=45	98.0 months Interval 34.5 to 130.7
The Estimated Value Represents the Percentage of Participants With a PR Confirmed CR+CCR, n=30	129.2 months Interval 98.3 to The SAS procedure was not able to calculate the upper limit of the confidence interval because there were too few events.
The Estimated Value Represents the Percentage of Participants With a PR Confirmed PR, n=13	6.9 months Interval 5.2 to 8.8
The Estimated Value Represents the Percentage of Participants With a PR Confirmed CR, n=27	130.7 months Interval 106.4 to The SAS procedure was not able to calculate the upper limit of the confidence interval because there were too few events.
The Estimated Value Represents the Percentage of Participants With a PR Confirmed CCR, n=2	11.8 months Interval 4.7 to 18.9

SECONDARY outcome

Timeframe: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)

Population: ITT-Exposed Population. Only those participants who died during the study due to any cause were assessed.

Overall survival is defined as the time from the treatment start date to the date of death from any cause.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=15 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Overall Survival	NA months The SAS procedure was not able to calculate the median or the confidence interval because there were too few events.

SECONDARY outcome

Timeframe: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)

Population: ITT-Exposed Population. Only those participants who experienced disease progression or died were assessed.

Time to progression is defined as the time from the treatment start date to the first documented progression or death. Progressive Disease is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=51 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Time to Progression of Disease or Death (Progression-free Survival)	74.3 months Interval 32.4 to 118.2

SECONDARY outcome

Timeframe: Baseline and up to 12 years (long-term follow up)

Population: ITT-Exposed Population. Only those participants who experienced any B-symptom at Baseline were assessed. Not all participants experienced all B-symptoms at Baseline; thus, the number of participants analyzed represents all participants who experienced at least one B-symptom.

The Ann Arbor staging system of lymphomas is used to summarize the extent of the cancer's spread. Stages are classified by Roman numerals I (less spread) to IV (more spread). If the following symptoms (called B-symptoms) are present, a "B" classification is added to the stage: night sweats, intermittant fever, and weight loss. B-symptoms indicate the presence of systemic symptoms. The presence or absence of B-symptoms has prognostic significance and is reflected in the staging of these lymphomas.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=11 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study Night sweats, n=8	8 participants
Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study Intermittant fever, n=3	3 participants
Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study Weight loss, n=4	4 participants

SECONDARY outcome

Timeframe: Baseline and up to 12 years (long-term follow up)

Population: ITT-Exposed Population. Only those participants with a PCR-positive status at Baseline were assessed. One participant had a Baseline measurement but no post Baseline measure, and was thus not assessed.

PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=40 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants Who Were Polymerase Chain Reaction (PCR)-Positive at Baseline With Bone Marrow Conversion to a Status of PCR Positive and Negative Any Time After Treatment PCR Positive after treatment	1 participants
Number of Participants Who Were Polymerase Chain Reaction (PCR)-Positive at Baseline With Bone Marrow Conversion to a Status of PCR Positive and Negative Any Time After Treatment PCR Negative after treatment	38 participants

SECONDARY outcome

Timeframe: Baseline and up to 12 years (long-term follow up)

Population: ITT-Exposed Population. Only those participants who were PCR positive at Baseline and converted to a status of PCR negative were assessed.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=38 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment All responders (CR+CCR+PR), n=38	59.5 months Interval 26.9 to 106.4
Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment Complete responders (CR+CCR), n=30	98.2 months Interval 35.5 to The SAS procedure was not able to calculate the confidence interval because there were too few events.
Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment Partial responders, n=8	6.9 months Interval 4.4 to 10.6

SECONDARY outcome

Timeframe: Baseline and up to 12 years (long-term follow up)

Population: ITT-Exposed Population. Only those participants with a PCR status taken at Baseline were evaluated for PFS.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=73 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Progression-free Survival (PFS) Based on Participants' Baseline PCR Status PCR-negative participants, n=33	130.8 months Interval 70.3 to The SAS procedure was not able to calculate the upper limit of the confidence interval because there were too few events.
Progression-free Survival (PFS) Based on Participants' Baseline PCR Status PCR-positive participants, n=40	48.8 months Interval 20.7 to 100.0

SECONDARY outcome

Timeframe: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)

Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.

t1/2 alpha is the estimated initial or alpha phase half-life in a two-compartmental pharmacokinetic model. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=68 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Initial Half-life (t1/2alpha)	3.85 hours Standard Deviation 3.33

SECONDARY outcome

Timeframe: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)

Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.

t1/2 beta is the estimated terminal or beta phase half-life in a two-compartmental pharmacokinetic model. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=70 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Terminal Half-life (t1/2beta)	64.57 hours Standard Deviation 16.23

SECONDARY outcome

Timeframe: 0-120 hours and 0-infinity hours from the dosimetric dose (given only on Day 0) and 0-120 hours and 0-infinity hours from the therapeutic dose (given only on Day 7)

Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.

Area under the concentration-time curve for I-131 tositumomab from time 0 to 120 hours and time 0 to infinity hours (extrapolated) after the end of the dosimetric dose infusion was measured. Unit: %ID\*h/ml, where %ID/ml is the percentage of the injected dose per milliliter of blood. AUC measures how much drug is in the system over time after infusion.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=70 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Area Under the Curve (AUC) at 0 to 120 Hours and 0 to Infinity Hours AUC(0-infinity)	1.43 %ID*h/ml Standard Deviation 0.41
Area Under the Curve (AUC) at 0 to 120 Hours and 0 to Infinity Hours AUC(0-120)	1.03 %ID*h/ml Standard Deviation 0.26

SECONDARY outcome

Timeframe: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)

Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.

Clearance of I-131 tositumomab after intravenous administration was measured. The clearance of a drug measures the rate at which the drug is removed from the body after the dose.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=70 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Clearance Values	77.34 Milliliters per hour (ml/hr) Standard Deviation 28.73

SECONDARY outcome

Timeframe: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)

Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.

Cmax is the maximum observed I-131 tositumomab concentration from time zero (end of the dosimetric dose infusion) to 120 hours after the end of the infusion. Unit: %ID/ml, where %ID/ml is the percentage of the injected dose per milliliter of blood. Cmax is the highest drug concentration in the blood after infusion.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=70 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Maximum Concentration (Cmax) Values	0.020 %ID/ml Standard Deviation 0.005

SECONDARY outcome

Timeframe: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)

Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.

Volume of distribution at the start of infusion and at steady state of I-131 tositumomab. The volume of distribution measures how much the drug spreads through the body after the dose. Steady state is defined as that state at which the overall intake of a drug is fairly in dynamic equilibrium with its elimination.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=70 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Volume of Distribution at Infusion Time 0 (Vd0) and Steady State (Vdss) Vd0	5297 milliliters (ml) Standard Deviation 1123
Volume of Distribution at Infusion Time 0 (Vd0) and Steady State (Vdss) Vdss	6710 milliliters (ml) Standard Deviation 1700

SECONDARY outcome

Timeframe: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)

Population: ITT-Exposed Population

Total body EHL is the time required for a radioactive element in the body to be diminished by 50% as a result of radioactive decay and biologic elimination. The EHL is equal to the product of the biologic half-life (BHL) and the radioactive half-life (RHL) divided by the sum of the BHL and the RHL: EHL=(BHL \* RHL)/(BHL + RHL). BHL is the time it takes for a drug to lose half of its pharmacologic, physiologic, or radiologic activity. RHL is the time taken for half of the radioactive nuclei to decay.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Total Body Effective Half-life (EHL)	63.6 hours Standard Deviation 8.44

SECONDARY outcome

Timeframe: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)

Population: ITT-Exposed Population. Only those participants who had available gamma camera images for the indicated organs were assessed.

Organ dosimetry was performed in participants using the kidneys, liver, lungs, spleen, red marrow, urinary bladder, and the remainder of the body as source organs. Organ doses and Iodine I-131 Anti-B1 Antibody biodistribution were comparable across the three Anti-B1 Antibody manufacturers. Gamma camera images of participants were used to calculate the amount of radiation that accumulated in the target tumor and normal organs (tumor/organ dosimetry). For the spleen (corrected) category, participant-specific corrections were made to account for individual spleen size.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Normal Organ Dosimetry for the Indicated Organs Spleen, n=74	835.92 cGy/75 cGy total body dose (TBD) Standard Deviation 358.610
Normal Organ Dosimetry for the Indicated Organs Spleen (corrected), n=72	393.38 cGy/75 cGy total body dose (TBD) Standard Deviation 120.602
Normal Organ Dosimetry for the Indicated Organs Blood, n=76	364.60 cGy/75 cGy total body dose (TBD) Standard Deviation 64.608
Normal Organ Dosimetry for the Indicated Organs Red Bone Marrow, n=41	105.57 cGy/75 cGy total body dose (TBD) Standard Deviation 10.342
Normal Organ Dosimetry for the Indicated Organs Thyroid, n=76	59.50 cGy/75 cGy total body dose (TBD) Standard Deviation 3.170
Normal Organ Dosimetry for the Indicated Organs Urine Bladder Wall, n=76	214.28 cGy/75 cGy total body dose (TBD) Standard Deviation 38.563
Normal Organ Dosimetry for the Indicated Organs Gall Bladder Wall, n=76	89.39 cGy/75 cGy total body dose (TBD) Standard Deviation 3.929
Normal Organ Dosimetry for the Indicated Organs Tumor, n=61	835.86 cGy/75 cGy total body dose (TBD) Standard Deviation 499.817
Normal Organ Dosimetry for the Indicated Organs Liver, n=76	221.69 cGy/75 cGy total body dose (TBD) Standard Deviation 43.721
Normal Organ Dosimetry for the Indicated Organs Kidney, n=75	637.35 cGy/75 cGy total body dose (TBD) Standard Deviation 129.360

SECONDARY outcome

Timeframe: From Baseline up to 12 years from the start of treatment (long-term follow up)

Population: ITT-Exposed Population

An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. A fatal SAE is a medical event that results in death.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants With the Indicated Fatal Serious Adverse Events (SAE)	1 participants

SECONDARY outcome

Timeframe: From Baseline up to 2 years from the start of treatment

Population: ITT-Exposed Population

Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants Evaluable and Not Evaluable for Human Anti-Murine Antibodies (HAMA) Evaluable	73 participants
Number of Participants Evaluable and Not Evaluable for Human Anti-Murine Antibodies (HAMA) Not evaluable	3 participants

SECONDARY outcome

Timeframe: From Baseline up to 2 years from the start of treatment

Population: ITT-Exposed Population. Only those participants who were evaluable for HAMA were assessed.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=73 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants With Conversion to HAMA Positivity Any Time During the Study From Baseline Negative	22 participants
Number of Participants With Conversion to HAMA Positivity Any Time During the Study From Baseline Positive	51 participants

SECONDARY outcome

Timeframe: From Baseline up to 2 years from the start of treatment

Population: ITT-Exposed Population. Only those participants who converted from being negative for HAMA at Baseline to being positive for HAMA any time following treatment were assessed.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=51 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Time to HAMA Positivity From the First Dosimetric Dose	93.5 days Standard Deviation 152.6

SECONDARY outcome

Timeframe: Baseline

Population: ITT-Exposed Population. Only those participants for whom TSH levels were recorded at Baseline were assessed.

TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were considered to have normal, high, or low TSH levels per the standard TSH ranges of the testing laboratory.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=73 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants With Elevated, Low, and Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline Elevated TSH at Baseline	4 participants
Number of Participants With Elevated, Low, and Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline Low/Normal TSH at Baseline	69 participants

SECONDARY outcome

Timeframe: Baseline and up to 12 years (long-term follow up)

Population: ITT-Exposed Population. Only participants with elevated TSH levels at Baseline were assessed.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=73 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Participants With Elevated TSH Levels at Baseline With Post Baseline TSH Levels of Low/Normal and Elevated Low/Normal TSH Post Baseline	61 participants
Participants With Elevated TSH Levels at Baseline With Post Baseline TSH Levels of Low/Normal and Elevated Elevated TSH Post Baseline	8 participants

SECONDARY outcome

Timeframe: Baseline and up to 12 years from the start of treatment

Population: ITT-Exposed Population. Only those participants who had low or normal TSH levels at Baseline and elevated levels post Baseline were assessed.

TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were categorized to have elevated or normal/low TSH values per the standard TSH ranges of the testing laboratory.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=8 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Time to Elevated TSH Post Baseline for Participants Who Had Low or Normal TSH Levels at Baseline and Elevated Levels Post Baseline	33.2 months Interval 5.9 to 106.2

SECONDARY outcome

Timeframe: Baseline and up to 12 years from the start of treatment

Population: ITT-Exposed Population

Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication. An AE is defined as any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered to be related to the medical treatment or procedure, that occurs during the course of the study.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants With the Adverse Event (AEs) of Hypothyroidism	8 participants

SECONDARY outcome

Timeframe: Baseline and up to 12 years from the start of treatment

Population: ITT-Exposed Population. Only those participants who had low or normal Baseline TSH levels were assessed.

Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=69 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants With Low or Normal Baseline TSH Levels That Developed Hypothyroidism	6 participants

SECONDARY outcome

Timeframe: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)

Population: ITT-Exposed Population

Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication.

Outcome measures

Outcome measures
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 Participants Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Number of Participants Who Received Thyroid Medication After Treatment	11 participants

Adverse Events

Tositumomab and Iodine I-131 Tositumomab

Serious events: 19 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 participants at risk Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Endocrine disorders Hyperthyroidism	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Endocrine disorders Hypothyroidism	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Abdominal pain	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Chest pain	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.

Other adverse events

Other adverse events
Measure	Tositumomab and Iodine I-131 Tositumomab n=76 participants at risk Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
General disorders Fatigue	53.9% 41/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Pyrexia	47.4% 36/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Chills	25.0% 19/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Oedema peripheral	11.8% 9/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Feeling cold	5.3% 4/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Influenza like illness	5.3% 4/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Local swelling	5.3% 4/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Pain	5.3% 4/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Axillary pain	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Feeling hot	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Malaise	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Chest discomfort	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Swelling	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Asthenia	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Catheter site pain	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Chest pain	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Discomfort	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Facial pain	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Gait disturbance	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Injection site irritation	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
General disorders Sensation of pressure	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Nausea	68.4% 52/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Vomiting	19.7% 15/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Diarrhoea	17.1% 13/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Constipation	10.5% 8/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Dyspepsia	7.9% 6/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Abdominal pain	6.6% 5/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Abdominal pain upper	6.6% 5/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Abdominal discomfort	5.3% 4/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Dysphagia	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Flatulence	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Abdominal distension	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Gastritis	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Mouth ulceration	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Aphthous stomatitis	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Cheilitis	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Dry mouth	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Faecal incontinence	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Glossodynia	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Haematemesis	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Hypoaesthesia oral	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Lip swelling	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Oral disorder	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Stomatitis	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Swollen tongue	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Tooth disorder	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Gastrointestinal disorders Toothache	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Myalgia	44.7% 34/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Arthralgia	43.4% 33/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Neck pain	13.2% 10/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Back pain	11.8% 9/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	11.8% 9/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Joint swelling	9.2% 7/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.9% 6/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Joint stiffness	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Muscular weakness	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Pain in jaw	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Headache	55.3% 42/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Dizziness	13.2% 10/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Dysgeusia	6.6% 5/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Paraesthesia	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Hypoaesthesia	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Somnolence	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Hyperaesthesia	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Lethargy	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Memory impairment	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Migraine	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Poor quality sleep	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Sensory disturbance	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Sinus headache	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Nervous system disorders Syncope	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Pruritus	36.8% 28/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Rash	17.1% 13/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Hyperhidrosis	15.8% 12/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Rash generalised	9.2% 7/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Urticaria	9.2% 7/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Rash pruritic	7.9% 6/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Erythema	5.3% 4/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Night sweats	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Swelling face	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Alopecia	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Rash erythematous	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Circumoral oedema	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Ecchymosis	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Exfoliative rash	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Pain of skin	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Palmar erythema	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Petechiae	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Photosensitivity reaction	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Pruritus generalised	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Rash papular	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Skin burning sensation	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Skin discolouration	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Skin lesion	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Skin odour abnormal	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Skin and subcutaneous tissue disorders Telangiectasia	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Metabolism and nutrition disorders Decreased appetite	52.6% 40/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Nasal congestion	15.8% 12/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Cough	7.9% 6/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.9% 6/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Throat irritation	7.9% 6/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Sinus congestion	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Sneezing	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Atelectasis	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Pharyngeal oedema	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Throat tightness	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Respiratory, thoracic and mediastinal disorders Wheezing	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Investigations White Blood Cells (WBC) < 2000 cells/cubic millimeter (CMM)	28.9% 22/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Investigations Absolute neutrophil count (ANC) < 1000 Cells/CMM	26.3% 20/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Investigations Platelets < 50000 cells/CMM	17.1% 13/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Upper respiratory tract infection	10.5% 8/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Nasopharyngitis	5.3% 4/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Sinusitis	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Diarrhoea infectious	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Folliculitis	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Fungal infection	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Gastroenteritis viral	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Herpes simplex	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Herpes zoster	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Influenza	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Laryngitis	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Oral herpes	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Pneumonia	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Rash pustular	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Respiratory tract infection viral	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Infections and infestations Rhinitis	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Psychiatric disorders Insomnia	15.8% 12/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Psychiatric disorders Anxiety	10.5% 8/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Psychiatric disorders Depression	3.9% 3/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Psychiatric disorders Agitation	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Psychiatric disorders Depressed mood	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Psychiatric disorders Emotional poverty	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Psychiatric disorders Hallucination	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Psychiatric disorders Nightmare	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Vascular disorders Flushing	13.2% 10/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Vascular disorders Hot flush	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Vascular disorders Hypotension	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Vascular disorders Hypertension	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Vascular disorders Peripheral coldness	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Blood and lymphatic system disorders Lymphadenopathy	10.5% 8/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Blood and lymphatic system disorders Lymph node pain	7.9% 6/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Conjunctivitis	9.2% 7/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Eye irritation	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Lacrimation increased	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Ocular hyperaemia	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Photophobia	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Vision blurred	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Conjunctival hyperaemia	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Eye oedema	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Eye pain	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Eye pruritus	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Eye swelling	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Eye disorders Eyelid oedema	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Investigations Body temperature increased	7.9% 6/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Investigations Blood pressure decreased	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Investigations Blood thyroid stimulating hormone increased	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Investigations Electrocardiogram abnormal	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Investigations Weight decreased	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Investigations Weight increased	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Reproductive system and breast disorders Menstruation irregular	6.6% 5/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Reproductive system and breast disorders Amenorrhoea	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Reproductive system and breast disorders Breast tenderness	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Reproductive system and breast disorders Menopausal symptoms	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Reproductive system and breast disorders Pelvic pain	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Reproductive system and breast disorders Vaginal haemorrhage	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Endocrine disorders Hypothyroidism	9.2% 7/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Endocrine disorders Hyperthyroidism	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Ear and labyrinth disorders Ear pruritus	6.6% 5/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Ear and labyrinth disorders Ear congestion	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Ear and labyrinth disorders Ear discomfort	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Injury, poisoning and procedural complications Procedural pain	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Injury, poisoning and procedural complications Contusion	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Injury, poisoning and procedural complications Forearm fracture	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Injury, poisoning and procedural complications Post procedural discomfort	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Injury, poisoning and procedural complications Wound	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Cardiac disorders Tachycardia	2.6% 2/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Cardiac disorders Aortic valve incompetence	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Cardiac disorders Atrioventricular block	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Cardiac disorders Mitral valve incompetence	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Cardiac disorders Palpitations	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Cardiac disorders Pericardial effusion	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Cardiac disorders Tricuspid valve incompetence	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Cardiac disorders Ventricular tachycardia	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Renal and urinary disorders Chromaturia	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Renal and urinary disorders Nocturia	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Renal and urinary disorders Urinary incontinence	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Renal and urinary disorders Urine odour abnormal	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	1.3% 1/76 • Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Study Day 0) until 12 years follow-up from the start of treatment.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER