Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-refractory Low-grade or Transformed Low-grade B-cell Non-Hodgkin's Lymphoma

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00989664
• Collaborator: (none)
• Enrollment: 60
• Arm: 1
• Duration (Months): 142

Study Details

Study Description

Brief Summary

The results from Phase 1/2 (RIT-I-000) and Phase 2 (RIT-II-001) studies of Tositumomab and Iodine I 131 Tositumomab (TST/I-131 TST) demonstrated that TST/ I-131 TST produced a high response rate in patients with chemotherapy-relapsed/refractory, low-grade or transformed low-grade Non-Hodgkin's Lymphoma (NHL). On the basis of these results this study was designed to compare the efficacy of TST/ I-131 TST to the last qualifying chemotherapy regimen in patients with chemotherapy-refractory, low-grade or transformed low-grade NHL.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin	Biological: Tositumomab and Iodine I 131 Tositumomab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter, Pivotal Phase III Study of Iodine-131 Anti-B1 Antibody (Murine) Radioimmunotherapy for Chemotherapy Refractory Low Grade B Cell Lymphomas and Low Grade Lymphomas That Have Transformed to Higher Grade Histologies
• Study Start Date: Nov 1, 1996
• Actual Primary Completion Date: Jan 1, 2004
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: open-label single arm Tositumomab and Iodine-131 Tositumomab radioimmunotherapy for chemotherapy-refractory low-grade B-cell lymphomas and low-grade lymphomas that have transformed to higher grade histologies.

Biological: Tositumomab and Iodine I 131 Tositumomab; Dosimetric Dose: 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by I-131 TST (35 mg of TST, of which 1-2 mg had been labeled with 5 mCi of Iodine-131) infused over 30 minutes (inclusive of a 10-minute flush). Therapeutic Dose: 7 to 14 days after the dosimetric dose, 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by I-131 TST (35 mg of TST labeled with enough Iodine-131 to administer the specified whole body radiation dose determined for the subject) infused over 30 minutes (inclusive of a 10-minute flush). The desired total body dose was 65 cGy for subjects with a baseline platelet count of 100,001-149,999/mm3 and 75 cGy for patients with a baseline platelet count ≥150,000/mm3. Obese patients received an attenuated dose by not including subject mass over 137% of their calculated lean body mass in their calculated lean body mass in the dose calculation.

Outcome Measures

Primary Outcome Measures

1. Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

   Par. with response are those with complete response (CR; complete resolution of all disease-related radiological abnormalities and the disappearance of all signs/symptoms related to disease), complete response unconfirmed (CRu; meets characteristics of CR, except the nodal size hasn't regressed sufficiently, or there is indeterminate bone marrow), or partial response (PR; >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions). Participants' LQCR was used as a comparator for subsequent treatment with Iodine I 131TST.

2. Duration of Response for Par. Receiving TST and I 131 TST With a Response >=30 Days Versus the Number of Par. With a Response >=30 Days After Their LQCR, as Assessed by the MIRROR Panel [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

   Duration of response is defined as the time from the first documented response (for par. with complete response, complete response unconfirmed, or partial response) until disease progression (DP). DP is defined as a >=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be >2 centimeters (cm) in diameter by radiographic evaluation or >1 cm in diameter by physical examination.

Secondary Outcome Measures

1. Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

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

2. Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

   Responses had to be confirmed by 2 separate evaluations occurring >=4 weeks apart. Par. with confirmed response include those with CR, CCR , or PR. A confirmed response (CR/CCR/PR) had to be confirmed by a consecutive response (>=28 days [ 4 weeks] later) that was the same or better. Individual confirmed response data only counts that response confirmed by the same response; thus, not all possible combinations are represented.

3. Time to Progression of Disease or Death, as Assessed by the Investigator [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

   Time to progression or progression-free survival is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death. Disease progression is defined as a >=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be >2 cm in diameter by radiographic evaluation or >1 cm in diameter by physical examination.

4. Time to Treatment Failure, as Assessed by the Investigator [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

   Time to treatment failure is defined as the length of time from the date of enrollment to the first incidence of treatment withdrawal, study removal, progression, and/or alternative therapy for the participant's lymphoma, or death.

5. Overall Survival [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

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

6. Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

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

7. Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

   An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the adverse event was related to study drug.

8. Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

   AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.

9. Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

   AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. The Investigator assessed whether the AE was possibly or probably related to study drug. In addition, all laboratory-derived hematologic toxicities (values outside the normal range) were assumed to be possibly or probably related to study drug.

10. Number of Participants With the Indicated Primary Cause of Death [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    The primary cause of death of the participants was assessed by the Investigator.

11. Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    Time to death from the last dose of study drug is the time period difference between when study drug treatment stopped and when death occurred.

12. Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    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. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgment.

13. Number of Participants With the Indicated Fatal SAEs Related to Study Drug [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    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. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious AEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.

14. Number of Participants With the Indicated SAEs Related to Study Drug [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    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. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.

15. Number of Participants With the Indicated Type of Infection [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen. The culture results could be positive or negative. The positive culture results indicate that the tested participant has the infection under investigation, in which case therapeutic treatment with anti-infective is required.

16. Number of Participants With an Infection for Which Anti-infectives Were Administered [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    Anti-infectives are capable of acting against infection, by inhibiting the spread of an infectious agent or by killing the infectious agent outright. Anti-infective is a general term that encompasses antibacterials, antibiotics, antifungals, antiprotozoans, and antivirals.

17. Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose [HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    The administration of murine antibodies may form HAMA. A HAMA assay was performed using the ImmunoSTRIP HAMA IgG enzyme-linked immune absorbent assay by a central laboratory (Covance Classic Laboratory Services, Indianapolis, IN). Fludarabine, a known immunosuppressant, might decrease HAMA production in addition to reducing bone marrow involvement. To be "positive," a participant had to have a positive HAMA assessment at any follow-up visit.

18. Time to HAMA Positivity From the First Dosimetric Dose [HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    HAMA are human immunoglobulins with specificity for mouse immunoglobulins. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment. Time to HAMA positivity was calculated as the difference between the day on which HAMA positivity occurred and the first dosimetric dose administration day.

19. Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event. Grade 3/4 hematological toxicities: hemoglobin <8.0 g/dL; platelets <50,000 cells per millimeters (mm)^3; ANC <1000 cells per mm^3; WBC <2000 cells per mm^3.

20. Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose [Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

    Thyroid function was determined periodically, including during follow-up, in order to assess if there was any effect of the Iodine 131 on thyroid function. Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female subjects ≥18 years of age with histologically confirmed at initial diagnosis, previously treated (at least 2 prior chemotherapy regimens), low-grade NHL or low-grade lymphoma that had transformed to intermediate- or high-grade histology.

Exclusion Criteria:

• Subjects with more than an average of 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically within 42 days of study entry. Bilateral posterior iliac crest core biopsies are required if the percentage of intratrebecular space involved exceeds 10% in a unilateral biopsy. The mean of bilateral biopsies must be no more than 25%.

• Cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks prior to study entry or persistent clinical evidence of toxicity.

• Prior stem cell transplant.

• Active obstructive hydronephrosis.

• Evidence of active infection requiring intravenous (IV) antibiotics at the time of study entry.

• New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation.

• Prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for 5 years.

• Known HIV infection.

• Known brain or leptomeningeal metastases.

• Subjects who are pregnant or nursing.

• Previous allergic reactions to iodine. This does not include reactions to intravenous iodine-containing contrast materials.

• Prior exposure to monoclonal or polyclonal antibodies of any non-human species for either diagnostic or therapeutic purposes, including engineered chimeric and humanized antibodies.

• Prior radioimmunotherapy.

• Progressive disease within 1 year of irradiation arising in a field that has been previously irradiated with >3500 cGy.

• Current use of either approved or non-approved (through another protocol) anti-cancer drugs or biologics

• De novo intermediate- or high-grade lymphoma.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L, Lister TA, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ, Vose JM. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2001 Oct 1;19(19):3918-28.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00989664
• Other Study ID Numbers: 104504
• First Posted: Oct 5, 2009
• Last Update Posted: Dec 13, 2016
• Last Verified: Oct 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: non-Hodgkin's Lymphoma; radioimmunotherapy; NHL; Bexxar; lymphoma; Tositumomab
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Tositumomab I-131

Study Results

Participant Flow

Pre-assignment Detail	Participants (par.) received radioimmunotherapy of tositumomab (TST) and Iodine I 131 TST in 2 phases (Ph.): Ph. 1, dosimetric dose; Ph. 2, therapeutic dose. Par. were evaluated until disease progression, they died, or they were on study for 2 years. Par. completing 2 years of study could enter a long-term follow-up study (BEX104526; NCT00240591).

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Period Title: Dosimetric and Therapeutic Treatment
STARTED	61
COMPLETED	0
NOT COMPLETED	61
Period Title: Dosimetric and Therapeutic Treatment
STARTED	14
COMPLETED	11
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Overall Participants	60
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.4 (10.5)
Gender (Count of Participants)
Female	22 36.7%
Male	38 63.3%
Race/Ethnicity, Customized (participants) [Number]
White	58 96.7%
Hispanic	1 1.7%
Black	1 1.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel
Description	Par. with response are those with complete response (CR; complete resolution of all disease-related radiological abnormalities and the disappearance of all signs/symptoms related to disease), complete response unconfirmed (CRu; meets characteristics of CR, except the nodal size hasn't regressed sufficiently, or there is indeterminate bone marrow), or partial response (PR; >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions). Participants' LQCR was used as a comparator for subsequent treatment with Iodine I 131TST.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population

Arm/Group Title	TST and I 131 TST	LQCR
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.	Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Measure Participants	60	60
Number [participants]	26 43.3%	5 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TST and I 131 TST, LQCR
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	McNemar
	Comments

2. Primary Outcome

Title	Duration of Response for Par. Receiving TST and I 131 TST With a Response >=30 Days Versus the Number of Par. With a Response >=30 Days After Their LQCR, as Assessed by the MIRROR Panel
Description	Duration of response is defined as the time from the first documented response (for par. with complete response, complete response unconfirmed, or partial response) until disease progression (DP). DP is defined as a >=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be >2 centimeters (cm) in diameter by radiographic evaluation or >1 cm in diameter by physical examination.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Only those participants with complete response, complete response unconfirmed, or partial response were analyzed.

Arm/Group Title	TST and I 131 TST	LQCR
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.	Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Measure Participants	33	17
Median (95% Confidence Interval) [months]	6.5	3.5

3. Secondary Outcome

Title	Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator
Description	Participants with response include those with CR, CCR, or PR. Criteria for CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Criteria for CCR: complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Criteria for PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Only those participants evaluable for response were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	59
Response (CR, CCR, or PR)	39 65%
CR	11 18.3%
CCR	1 1.7%
CR+CCR	12 20%
PR	27 45%

4. Secondary Outcome

Title	Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator
Description	Responses had to be confirmed by 2 separate evaluations occurring >=4 weeks apart. Par. with confirmed response include those with CR, CCR , or PR. A confirmed response (CR/CCR/PR) had to be confirmed by a consecutive response (>=28 days [ 4 weeks] later) that was the same or better. Individual confirmed response data only counts that response confirmed by the same response; thus, not all possible combinations are represented.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Only those participants evaluable for confirmed response were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	50
Confirmed Response (CR, CCR, or PR)	30 50%
CR	9 15%
CCR	1 1.7%
CR+CCR	11 18.3%
PR	18 30%

5. Secondary Outcome

Title	Time to Progression of Disease or Death, as Assessed by the Investigator
Description	Time to progression or progression-free survival is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death. Disease progression is defined as a >=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be >2 cm in diameter by radiographic evaluation or >1 cm in diameter by physical examination.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Only those participants who experienced disease progression or died were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	54
Median (95% Confidence Interval) [months]	4.7

6. Secondary Outcome

Title	Time to Treatment Failure, as Assessed by the Investigator
Description	Time to treatment failure is defined as the length of time from the date of enrollment to the first incidence of treatment withdrawal, study removal, progression, and/or alternative therapy for the participant's lymphoma, or death.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Only those participants who experienced treatment failure were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	54
Median (95% Confidence Interval) [months]	4.6

7. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from the treatment start date to the date of death from any cause.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Only those participants who died during the study and during the follow-up period were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	48
Median (95% Confidence Interval) [months]	30.1

8. Secondary Outcome

Title	Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator
Description	Participants with response include those with CR, CCR, or PR. Criteria for CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Criteria for CCR: complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Criteria for PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Only those participants evaluable for response were analyzed.

Arm/Group Title	TST and I 131 TST	LQCR
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.	Participants treated with at least two chemotherapy regimens before enrolling in study BEX104504
Measure Participants	59	60
Response (CR, CCR, or PR)	39 65%	17 NaN
CR	11 18.3%	1 NaN
CCR	1 1.7%	1 NaN
CR+CCR	12 20%	2 NaN
PR	27 45%	15 NaN

9. Secondary Outcome

Title	Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants
Description	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the adverse event was related to study drug.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. All participants who experienced any AE related to study drug were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	57
Absolute Neutrophil Count (ANC) <1000 cells/cm^3	35 58.3%
Platelets <50000 cells/cm^3	29 48.3%
White Blood Cells (WBC) <2000 cells/cm^3	29 48.3%
Hemoglobin <8.0 grams/deciliter (g/dL)	13 21.7%
Fatigue	27 45%
Pyrexia	19 31.7%
Chills	11 18.3%
Nausea	16 26.7%
Vomiting	9 15%
Diarrhoea	4 6.7%
Thrombocytopenia	10 16.7%
Neutropenia	9 15%
Anaemia	7 11.7%
Leukopenia	4 6.7%
Pruritus	8 13.3%
Rash	4 6.7%
Night sweats	3 5%
Cough	7 11.7%
Dyspnoea	7 11.7%
Throat irritation	4 6.7%
Productive cough	3 5%
Headache	5 8.3%
Dizziness	3 5%
Somnolence	3 5%
Decreased appetite	11 18.3%
Arthralgia	5 8.3%
Myalgia	5 8.3%
Pain in extremity	3 5%
Myelodysplastic syndrome	4 6.7%
Hypothyroidism	7 11.7%
Hypotension	5 8.3%
Tachycardia	3 5%

10. Secondary Outcome

Title	Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants
Description	AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. All participants who experienced Grade 3 or Grade 4 AEs were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	51
ANC <1000 cells/cm^3	35 58.3%
Platelets <50000 cells/cm^3	29 48.3%
WBC <2000 cells/cm^3	29 48.3%
Hemoglobin <8.0 g/dL	13 21.7%
Myelodysplastic syndrome	4 6.7%
Neutropenia	9 15%
Thrombocytopenia	8 13.3%
Anaemia	4 6.7%
Leukopenia	3 5%
Dyspnoea	3 5%
Pleural effusion	3 5%

11. Secondary Outcome

Title	Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants
Description	AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. The Investigator assessed whether the AE was possibly or probably related to study drug. In addition, all laboratory-derived hematologic toxicities (values outside the normal range) were assumed to be possibly or probably related to study drug.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. All participants who experienced Grade 3 or 4 AEs related to study drug were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	46
ANC <1000 cells/cm^3	35 58.3%
Platelets <50000 cells/cm^3	29 48.3%
WBC <2000 cells/cm^3	29 48.3%
Hemoglobin <8.0 g/dL	13 21.7%
Neutropenia	9 15%
Thrombocytopenia	8 13.3%
Anaemia	4 6.7%
Leukopenia	3 5%
Myelodysplastic syndrome	4 6.7%

12. Secondary Outcome

Title	Number of Participants With the Indicated Primary Cause of Death
Description	The primary cause of death of the participants was assessed by the Investigator.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. All participants who died during the study were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	48
Progression of lymphoma	37 61.7%
Complications related to study drug	0 0%
Other	11 18.3%

13. Secondary Outcome

Title	Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug
Description	Time to death from the last dose of study drug is the time period difference between when study drug treatment stopped and when death occurred.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. All participants who died during the study were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	48
<=30 Days	1 1.7%
>30 Days	47 78.3%

14. Secondary Outcome

Title	Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug
Description	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. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgment.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. All participants who experienced fatal SAEs were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	10
Pneumonia aspiration	1 1.7%
Non-Hodgkins lymphoma	2 3.3%
Encephalopathy	1 1.7%
Dyspnea	1 1.7%

15. Secondary Outcome

Title	Number of Participants With the Indicated Fatal SAEs Related to Study Drug
Description	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. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious AEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. All participants who experienced fatal SAEs were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	10
Lung adenocarcinoma	1 1.7%
Myelodysplastic syndrome	2 3.3%
Encephalopathy	1 1.7%
Pulmonary hemorrhage	1 1.7%

16. Secondary Outcome

Title	Number of Participants With the Indicated SAEs Related to Study Drug
Description	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. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. All participants who experienced SAEs were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	19
Myelodysplastic syndrome	4 6.7%
Squamous cell carcinoma	2 3.3%
Basal cell carcinoma	1 1.7%
Colon cancer stage 0	1 1.7%
Lung adenocarcinoma	1 1.7%
Refractory anaemia with an excess of blasts	1 1.7%
Squamous cell carcinoma of skin	1 1.7%
Anaemia	2 3.3%
Leukopenia	1 1.7%
Neutropenia	1 1.7%
Chronic obstructive pulmonary disease	1 1.7%
Dyspnoea	1 1.7%
Pulmonary haemorrhage	1 1.7%
Pneumocystis jiroveci pneumonia	1 1.7%
Pneumonia	1 1.7%
Atrial flutter	1 1.7%
Subdural haematoma	1 1.7%
Arthralgia	1 1.7%
Encephalopathy	1 1.7%

17. Secondary Outcome

Title	Number of Participants With the Indicated Type of Infection
Description	An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen. The culture results could be positive or negative. The positive culture results indicate that the tested participant has the infection under investigation, in which case therapeutic treatment with anti-infective is required.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Only those participants who experienced any infection were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	59
Any Infection; n=59	15 25%
No Infection; n=59	44 73.3%
Sepsis; n=15	0 0%
Pneumonia; n=15	5 8.3%
Other Infections; n=15	14 23.3%

18. Secondary Outcome

Title	Number of Participants With an Infection for Which Anti-infectives Were Administered
Description	Anti-infectives are capable of acting against infection, by inhibiting the spread of an infectious agent or by killing the infectious agent outright. Anti-infective is a general term that encompasses antibacterials, antibiotics, antifungals, antiprotozoans, and antivirals.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Only those participants who had an infection during the study and during the follow-up period were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	15
Anti-infective Administered	12 20%
Anti-infective Not Administered	3 5%

19. Secondary Outcome

Title	Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose
Description	The administration of murine antibodies may form HAMA. A HAMA assay was performed using the ImmunoSTRIP HAMA IgG enzyme-linked immune absorbent assay by a central laboratory (Covance Classic Laboratory Services, Indianapolis, IN). Fludarabine, a known immunosuppressant, might decrease HAMA production in addition to reducing bone marrow involvement. To be "positive," a participant had to have a positive HAMA assessment at any follow-up visit.
Time Frame	HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Only those participants evaluable for HAMA were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	58
Positive	5 8.3%
Negative	53 88.3%

20. Secondary Outcome

Title	Time to HAMA Positivity From the First Dosimetric Dose
Description	HAMA are human immunoglobulins with specificity for mouse immunoglobulins. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment. Time to HAMA positivity was calculated as the difference between the day on which HAMA positivity occurred and the first dosimetric dose administration day.
Time Frame	HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Participants who converted from being negative for HAMA at Baseline to being positive for HAMA following treatment were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	5
Median (Full Range) [days]	279

21. Secondary Outcome

Title	Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities
Description	Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event. Grade 3/4 hematological toxicities: hemoglobin <8.0 g/dL; platelets <50,000 cells per millimeters (mm)^3; ANC <1000 cells per mm^3; WBC <2000 cells per mm^3.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	60
ANC	35 58.3%
Hemoglobin	13 21.7%
Platelets	29 48.3%
WBC count	29 48.3%

22. Secondary Outcome

Title	Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose
Description	Thyroid function was determined periodically, including during follow-up, in order to assess if there was any effect of the Iodine 131 on thyroid function. Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.
Time Frame	Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Outcome Measure Data

Analysis Population Description

ITT Exposed Population. Participants who were evaluable for thyroid function assessment were analyzed.

Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Measure Participants	52
Prior to therapy	8 13.3%
After therapeutic dose	7 11.7%

Adverse Events

Time Frame	Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Arm/Group Title	TST and I 131 TST
Arm/Group Description	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
All Cause Mortality
	TST and I 131 TST
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	TST and I 131 TST
	Affected / at Risk (%)	# Events
Total	30/60 (50%)
Blood and lymphatic system disorders
Anaemia	2/60 (3.3%)
Leukopenia	1/60 (1.7%)
Neutropenia	1/60 (1.7%)
Cardiac disorders
Atrial flutter	1/60 (1.7%)
Cardiomegaly	1/60 (1.7%)
Endocrine disorders
Hypercalcaemia of malignancy	1/60 (1.7%)
Gastrointestinal disorders
Abdominal distension	1/60 (1.7%)
Constipation	1/60 (1.7%)
Dysphagia	1/60 (1.7%)
Nausea	1/60 (1.7%)
Vomiting	1/60 (1.7%)
Infections and infestations
Pneumonia	2/60 (3.3%)
Bronchitis	1/60 (1.7%)
Device related sepsis	1/60 (1.7%)
Pneumocystis jiroveci pneumonia	1/60 (1.7%)
Injury, poisoning and procedural complications
Hip fracture	1/60 (1.7%)
Subdural haematoma	1/60 (1.7%)
Metabolism and nutrition disorders
Dehydration	1/60 (1.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/60 (1.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome	4/60 (6.7%)
Squamous cell carcinoma	3/60 (5%)
Basal cell carcinoma	2/60 (3.3%)
Non-Hodgkin's lymphoma	2/60 (3.3%)
Squamous cell carcinoma of skin	2/60 (3.3%)
Colon cancer stage 0	1/60 (1.7%)
Lung adenocarcinoma	1/60 (1.7%)
Lymphoma	1/60 (1.7%)
Malignant ascites	1/60 (1.7%)
Refractory anaemia with an excess of blasts	1/60 (1.7%)
Skin cancer	1/60 (1.7%)
Nervous system disorders
Encephalopathy	2/60 (3.3%)
Renal and urinary disorders
Nephropathy	1/60 (1.7%)
Renal failure	1/60 (1.7%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	3/60 (5%)
Dyspnoea	2/60 (3.3%)
Chronic obstructive pulmonary disease	1/60 (1.7%)
Pneumonia aspiration	1/60 (1.7%)
Pulmonary haemorrhage	1/60 (1.7%)
Vascular disorders
Deep vein thrombosis	1/60 (1.7%)
Orthostatic hypotension	1/60 (1.7%)
Superior vena caval occlusion	1/60 (1.7%)
Other (Not Including Serious) Adverse Events
	TST and I 131 TST
	Affected / at Risk (%)	# Events
Total	59/60 (98.3%)
Blood and lymphatic system disorders
Thrombocytopenia	10/60 (16.7%)
Neutropenia	8/60 (13.3%)
Anaemia	6/60 (10%)
Leukopenia	3/60 (5%)
Lymph node pain	2/60 (3.3%)
Lymphadenopathy	2/60 (3.3%)
Febrile neutropenia	1/60 (1.7%)
Lymphatic disorder	1/60 (1.7%)
Cardiac disorders
Tachycardia	6/60 (10%)
Palpitations	1/60 (1.7%)
Ear and labyrinth disorders
Tinnitus	2/60 (3.3%)
Ear pain	1/60 (1.7%)
Endocrine disorders
Hypothyroidism	7/60 (11.7%)
Eye disorders
Conjunctivitis	1/60 (1.7%)
Diplopia	1/60 (1.7%)
Dry eye	1/60 (1.7%)
Eye oedema	1/60 (1.7%)
Vision blurred	1/60 (1.7%)
Visual impairment	1/60 (1.7%)
Gastrointestinal disorders
Nausea	21/60 (35%)
Diarrhoea	13/60 (21.7%)
Vomiting	12/60 (20%)
Abdominal pain	8/60 (13.3%)
Constipation	5/60 (8.3%)
Abdominal discomfort	3/60 (5%)
Abdominal pain upper	3/60 (5%)
Abdominal distension	2/60 (3.3%)
Dyspepsia	2/60 (3.3%)
Abdominal pain lower	1/60 (1.7%)
Diverticulum	1/60 (1.7%)
Gastritis	1/60 (1.7%)
Gastrooesophageal reflux disease	1/60 (1.7%)
Haemorrhoids	1/60 (1.7%)
Stomatitis	1/60 (1.7%)
Tongue ulceration	1/60 (1.7%)
General disorders
Fatigue	29/60 (48.3%)
Pyrexia	22/60 (36.7%)
Chills	11/60 (18.3%)
Asthenia	6/60 (10%)
Oedema peripheral	6/60 (10%)
Chest pain	4/60 (6.7%)
Pain	3/60 (5%)
Chest discomfort	2/60 (3.3%)
Oedema	2/60 (3.3%)
Early satiety	1/60 (1.7%)
Feeling cold	1/60 (1.7%)
Feeling jittery	1/60 (1.7%)
Hunger	1/60 (1.7%)
Infusion site extravasation	1/60 (1.7%)
Malaise	1/60 (1.7%)
Nodule	1/60 (1.7%)
Swelling	1/60 (1.7%)
Immune system disorders
Multiple allergies	1/60 (1.7%)
Infections and infestations
Upper respiratory tract infection	5/60 (8.3%)
Bronchitis	4/60 (6.7%)
Herpes zoster	3/60 (5%)
Nasopharyngitis	3/60 (5%)
Oral herpes	2/60 (3.3%)
Sinusitis	2/60 (3.3%)
Bronchopulmonary aspergillosis	1/60 (1.7%)
Candidiasis	1/60 (1.7%)
Cellulitis	1/60 (1.7%)
Cytomegalovirus infection	1/60 (1.7%)
Ear infection	1/60 (1.7%)
Gastroenteritis viral	1/60 (1.7%)
Haemophilus infection	1/60 (1.7%)
Infection	1/60 (1.7%)
Influenza	1/60 (1.7%)
Keratitis herpetic	1/60 (1.7%)
Oral candidiasis	1/60 (1.7%)
Parainfluenzae virus infection	1/60 (1.7%)
Pneumonia	1/60 (1.7%)
Rash pustular	1/60 (1.7%)
Rhinitis	1/60 (1.7%)
Urinary tract infection	1/60 (1.7%)
Injury, poisoning and procedural complications
Upper limb fracture	2/60 (3.3%)
Contusion	1/60 (1.7%)
Febrile nonhaemolytic transfusion reaction	1/60 (1.7%)
Incisional hernia	1/60 (1.7%)
Rib fracture	1/60 (1.7%)
Skin laceration	1/60 (1.7%)
Transfusion reaction	1/60 (1.7%)
Investigations
ANC < 1,000 cells/mm^3	35/60 (58.3%)
Platelets <50000 cells/mm^3	29/60 (48.3%)
WBC < 2000 cells/mm^3	29/60 (48.3%)
Hemoglobin < 8.0 g/dL	13/60 (21.7%)
Weight decreased	4/60 (6.7%)
Blood pressure decreased	1/60 (1.7%)
Blood thyroid stimulating hormone increased	1/60 (1.7%)
Ejection fraction decreased	1/60 (1.7%)
Haemoglobin decreased	1/60 (1.7%)
Heart sounds abnormal	1/60 (1.7%)
Occult blood positive	1/60 (1.7%)
Respiratory rate increased	1/60 (1.7%)
Weight increased	1/60 (1.7%)
Metabolism and nutrition disorders
Decreased appetite	15/60 (25%)
Dehydration	1/60 (1.7%)
Folate deficiency	1/60 (1.7%)
Hypercalcaemia	1/60 (1.7%)
Hyperkalaemia	1/60 (1.7%)
Hypoglycaemia	1/60 (1.7%)
Hypokalaemia	1/60 (1.7%)
Hyponatraemia	1/60 (1.7%)
Musculoskeletal and connective tissue disorders
Myalgia	6/60 (10%)
Pain in extremity	6/60 (10%)
Back pain	5/60 (8.3%)
Arthralgia	4/60 (6.7%)
Neck pain	4/60 (6.7%)
Groin pain	2/60 (3.3%)
Joint swelling	2/60 (3.3%)
Musculoskeletal chest pain	2/60 (3.3%)
Arthritis	1/60 (1.7%)
Bone lesion	1/60 (1.7%)
Mobility decreased	1/60 (1.7%)
Muscle atrophy	1/60 (1.7%)
Muscle spasms	1/60 (1.7%)
Musculoskeletal pain	1/60 (1.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myeloproliferative disorder	1/60 (1.7%)
Nervous system disorders
Headache	7/60 (11.7%)
Somnolence	6/60 (10%)
Dizziness	4/60 (6.7%)
Amnesia	1/60 (1.7%)
Carpal tunnel syndrome	1/60 (1.7%)
Dysgeusia	1/60 (1.7%)
Hypoaesthesia	1/60 (1.7%)
Memory impairment	1/60 (1.7%)
Mental impairment	1/60 (1.7%)
Neuropathy peripheral	1/60 (1.7%)
Peroneal nerve palsy	1/60 (1.7%)
Sinus headache	1/60 (1.7%)
Tremor	1/60 (1.7%)
VIIth nerve paralysis	1/60 (1.7%)
Psychiatric disorders
Depression	3/60 (5%)
Anxiety	2/60 (3.3%)
Insomnia	2/60 (3.3%)
Boredom	1/60 (1.7%)
Confusional state	1/60 (1.7%)
Tearfulness	1/60 (1.7%)
Renal and urinary disorders
Dysuria	1/60 (1.7%)
Hydronephrosis	1/60 (1.7%)
Micturition urgency	1/60 (1.7%)
Nocturia	1/60 (1.7%)
Renal failure	1/60 (1.7%)
Reproductive system and breast disorders
Breast pain	1/60 (1.7%)
Respiratory, thoracic and mediastinal disorders
Cough	13/60 (21.7%)
Dyspnoea	6/60 (10%)
Productive cough	6/60 (10%)
Nasal congestion	4/60 (6.7%)
Throat irritation	4/60 (6.7%)
Epistaxis	3/60 (5%)
Oropharyngeal pain	3/60 (5%)
Rhinorrhoea	2/60 (3.3%)
Wheezing	2/60 (3.3%)
Asthma	1/60 (1.7%)
Bronchospasm	1/60 (1.7%)
Dysphonia	1/60 (1.7%)
Dysphonia exertional	1/60 (1.7%)
Nasal oedema	1/60 (1.7%)
Pneumothorax	1/60 (1.7%)
Respiratory tract congestion	1/60 (1.7%)
Upper respiratory tract congestion	1/60 (1.7%)
Upper-airway cough syndrome	1/60 (1.7%)
Skin and subcutaneous tissue disorders
Pruritus	8/60 (13.3%)
Night sweats	6/60 (10%)
Rash	4/60 (6.7%)
Erythema	2/60 (3.3%)
Urticaria	2/60 (3.3%)
Decubitus ulcer	1/60 (1.7%)
Hyperhidrosis	1/60 (1.7%)
Petechiae	1/60 (1.7%)
Rash erythematous	1/60 (1.7%)
Rash vesicular	1/60 (1.7%)
Swelling face	1/60 (1.7%)
Vascular disorders
Hypotension	6/60 (10%)
Deep vein thrombosis	2/60 (3.3%)
Flushing	2/60 (3.3%)
Aortic stenosis	1/60 (1.7%)
Thrombophlebitis	1/60 (1.7%)
Thrombosis	1/60 (1.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.