Safety and Efficacy Study of Iodine-131 Anti-B1 Antibody Plus CHOP For Untreated Mantle Cell Lymphoma

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00992992
• Collaborator: (none)
• Enrollment: 25
• Arm: 1
• Actual Duration (Months): 144.1

Study Details

Study Description

Brief Summary

The primary efficacy endpoint of this study is to determine the duration of response of the sequential administration of Iodine-131 Anti-B1 Antibody followed by six cycles of CHOP for patients with previously untreated Mantle Cell Lymphoma (MCL). The secondary efficacy endpoints for this study are to determine the response rate, confirmed response rate, complete response rate, confirmed complete response rate, duration of response for confirmed responders, duration of response for complete responders, duration of response for confirmed complete responders, progression-free survival, time to treatment failure, and the predictive value of detection of minimal residual disease by molecular techniques on response duration. The pharmacokinetic endpoint is to determine the total body residence time of Iodine-131 Anti-B1 Antibody following the dosimetric dose. The safety endpoints are to determine the incidence of adverse experiences, hematologic toxicity, (e.g., nadir, time to nadir, and time to recovery), use of supportive care, percent of patients converting to human anti-murine antibody (HAMA) positivity, the effects of Iodine-131 Anti-B1 Antibody on the growth and function of hematopoietic progenitor cells, and survival of patients with previously untreated MCL treated with Iodine-131 Anti-B1 Antibody followed by six cycles of CHOP.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Mantle-Cell	Biological: Tositumomab and Iodine I 131 Tositumomab followed by CHOP	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study Of Iodine-131 Anti-B1 Antibody Plus CHOP For Patients With Previously Untreated Mantle Cell Lymphoma
• Actual Study Start Date: Jun 28, 2001
• Actual Primary Completion Date: Jun 30, 2013
• Actual Study Completion Date: Jun 30, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Tositumomab and Iodine I 131 Tositumomab followed by CHOP Tositumomab and Iodine I 131 Tositumomab followed by CHOP

Biological: Tositumomab and Iodine I 131 Tositumomab followed by CHOP; Patients will receive an infusion of unlabeled Tositumomab (450 mg) followed by an infusion of Tositumomab (35 mg) containing 5 mCi of Iodine-131 (dosimetric dose). Whole body gamma camera scans will be obtained on Day 0; Day 2, 3, or 4; and Day 6 or 7 following the dosimetric dose. Patients will then receive an infusion of unlabeled Tositumomab (450 mg) followed by an infusion of 35 mg Tositumomab containing a patient-specific dose of Iodine-131 calculated to deliver a 75 cGy total body radiation dose (therapeutic dose). Patients who have platelet counts of 100,000-149,000 cells/mm3 will receive 65 cGy; obese patients will be dosed based upon 137% of their lean body mass. Patients will be treated with a thyroid blocking agent 24 hours prior to the dosimetric dose and continuing for 14 days following the therapeutic dose. Approximately 13 weeks following the therapeutic dose, CHOP will be administered every 21 days for a total of 6 cycles.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With the Indicated Unconfirmed Response (Complete Response, Complete Response Unconfirmed, and Partial Response) [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

   Participants with response include those with complete response (CR: complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms), complete response unconfirmed (CRu: CR, with one of the following: residual lymph node mass >1.5 centimeters [cm] that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow), or partial response (PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).

Secondary Outcome Measures

1. Number of Participants With the Indicated Confirmed Response (Confirmed Complete Response, Complete Response Unconfirmed, and Partial Response) [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

   A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart. Participants with a confirmed response include those with complete response (CR: complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms), complete response unconfirmed (CRu: CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow), or partial response (PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions). The individual rows for confirmed CR, confirmed CRu, and confirmed PR represent confirmation of the same response. For example, a confirmed CR indicates that a CR was followed by another CR at least 4 weeks later.

2. Duration of Response for All Confirmed Responders (CR + CRu + PR) [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

   Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Complete response unconfirmed (CRu) is defined as CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow. Partial response (PR) is defined as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions. For participants with CR, CRu, or PR, duration of response is defined as the time from the first documented response to the first documented progression.

3. Duration of Response for All Unconfirmed Responders (CR + CRu + PR) [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

   Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Complete response unconfirmed is defined as CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow. Partial response (PR) is defind as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions. Duration of response is defined as the time from the first documented response to the first documented progression.

4. Duration of Response for Unconfirmed Complete Responders [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

   Complete response is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Duration of response is defined as the time from the first documented response to the first documented progression.

5. Duration of Response for Confirmed Complete Responders [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

   Complete response is the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart. Duration of response is defined as the time from the first documented response to the first documented progression.

6. Progression-free Survival [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

   Progression-free survival is defined as the time from the start of treatment (i.e., the dosimetric dose) to the first documented disease progression or death. Disease progression 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. Individual lesions must have been greater than 2 centimeters (cm) in diameter by radiographic evaluation or greater than 1 cm in diameter by physical examination.

7. Time to Treatment Failure [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

   Time to treatment failure is defined as the time from the date of the dosimetric dose to the first occurrence of treatment withdrawal, decision to seek additional therapy, study removal, disease progression, alternative therapy, or death.

8. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

   An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAEs are defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; resulted in disability; or was a congenital anomaly. Refer to the general AE/SAE module for a complete list of all AEs and SAEs.

9. Mean Nadir Value for Absolute Neutrophil Count (ANC) [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

   Nadir is defined as the lowest laboratory value recorded following the administration of study medication. ANC is a measure of the number of neutrophil granulocytes present in the blood. Neutrophils are a type of white blood cell that fights infection.

10. Mean Nadir Value for Hemoglobin [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

    Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells.

11. Mean Nadir Values for Platelets and White Blood Cell (WBC) Count [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

    Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Platelets and WBCs are types of blood cells.

12. Time to Nadir for the Indicated Hematology Parameters [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

    Hematology parameters include ANC (calculated), hemoglobin, platelet count, and WBC count. Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Time to nadir is defined as the time from Baseline to the time the lowest value recorded following the therapeutic dose.

13. Time to Recovery From the Indicated Hematology Parameters [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

    Hematology parameters include ANC (calculated), hemoglobin, platelet count, and WBC count. Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Time to recovery to Baseline for the indicated hematologic parameters is defined as the time required for recovery from nadir values to Baseline values.

14. Number of Participants Negative for Human Anti-Murine (Mouse) Antibody (HAMA) at Screening Who Converted to HAMA Positivity or Remained Negative During the Course of the Study [Screening; at Week 7, Week 13, then every 6 months until disease progression or death (up to 143 months)]

    The number of participants who developed human anti-murine (mouse) anibodies (HAMA) after treatment was measured. Conversion to HAMA positivity is relative to Screening (participants were evaluable for HAMA analysis if they were HAMA negative at Screening).

15. Number of Participants With an Adverse Event of Cytopenia [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

    The effects of iodine I-131 tositumomab on the growth and function of hematopoietic progenitor cells was measured as the number of participants who had cytopenia. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

16. Overall Survival [Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)]

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

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have a confirmed initial diagnosis of mantle cell non-Hodgkin's lymphoma by histology according to the WHO classification .

• Patients must have Ann Arbor bulky stage II, stage III, or stage IV disease at diagnosis. Bulky stage II disease is defined as a mediastinal mass greater than one-third of the maximum chest diameter, or any other mass greater than or equal to 10 cm in maximum diameter.

• Patients must have less than an average of 25% of the intratrabecular marrow space involved by NHL in bilateral bone marrow biopsy specimens as assessed microscopically at study entry. A unilateral bone marrow biopsy demonstrating <10% involvement with NHL is also adequate.

• Patients must have evidence that their tumor tissue expresses the CD20 antigen. Immunoperoxidase stains of paraffin-embedded tissue showing positive reactivity with L26 antibody or immunoperoxidase stains of frozen tissue showing positive reactivity with Anti-B1 Antibody (Coulter Clone) or similar commercially available CD20 antibody or evidence of CD20 positivity by flow cytometry are acceptable evidence of CD20 positivity. This must be performed within 42 days of study entry.

• Patients must have a performance status of at least 60% on the Karnofsky Performance Scale and an anticipated survival of at least 3 months.

• Patients must have an ANC greater than or equal to 1500 cells/mm3 and a platelet count greater than or equal to 100,000 cells/mm3 within 14 days of study enrollment. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products.

• Patients must have adequate renal function (defined as serum creatinine <1.5 times the upper limit of normal) and hepatic function (defined as total bilirubin <1.5 times the upper limit of normal and AST <5 times the upper limit of normal) within 14 days of study enrollment.

• Patients must have bi-dimensionally measurable disease. At least one lesion must be greater than or equal to 2.0 x 2.0 cm by computerized tomography scan.

• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.

• Patients must have a cardiac left ventricular ejection fraction of greater than or equal to 50% by ventriculography or echocardiogram.

Exclusion Criteria:

• Patients who have received prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for their MCL

• Patients with active obstructive hydronephrosis

• Patients with serious illness that would preclude evaluation

• Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years

• Patients with known HIV infection

• Patients who are HAMA positive

• Patients with known brain or leptomeningeal metastases.

• Patients who are pregnant or breastfeeding. Males and females must agree to use a contraceptive method while on study and for 6 months after receiving Iodine-131 Anti-B1 Antibody.

• Patients with active infection requiring IV anti-infectives at the time of study enrollment.

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

Publications

• Zelenetz AD, Popplewell LL, Noy A, Horner TJ, Lin TS, Donnelly G, Sgouros G, Rijo I, Divgi CR. Phase 2 Study of Iodine-131 Tositumomab Plus Chemotherapy in Patients With Previously Untreated Mantle-Cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2020 Nov;20(11):749-756.e1. doi: 10.1016/j.clml.2019.04.010. Epub 2019 Apr 29.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00992992
• Other Study ID Numbers: 393229/005
• First Posted: Oct 9, 2009
• Last Update Posted: Dec 4, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP); Tositumomab; Tositumomab and Iodine I-131 tostumomab; Bexxar; Iodine-131 Anti-B1 Antibody; Mantle Cell; radioimmunotherapy
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Tositumomab I-131

Study Results

Participant Flow

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Period Title: Overall Study
STARTED	25
COMPLETED	0
NOT COMPLETED	25

Baseline Characteristics

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Overall Participants	25
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.4 (9.6)
Sex: Female, Male (Count of Participants)
Female	2 8%
Male	23 92%
Race/Ethnicity, Customized (participants) [Number]
White	24 96%
Hispanic	1 4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With the Indicated Unconfirmed Response (Complete Response, Complete Response Unconfirmed, and Partial Response)
Description	Participants with response include those with complete response (CR: complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms), complete response unconfirmed (CRu: CR, with one of the following: residual lymph node mass >1.5 centimeters [cm] that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow), or partial response (PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population: all participants who received any iodine I-131 tositumomab or CHOP treatment. Only those participants evaluable for response (those with at least one response assessment) were analyzed.

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	24
CR	14 56%
CRu	2 8%
PR	5 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Iodine I-131 Tositumomab + CHOP
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	56
	Confidence Interval	(2-Sided) 95%; 37 to 75
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value reflects the percentage of participants with unconfirmed complete response (CR).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Iodine I-131 Tositumomab + CHOP
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	8
	Confidence Interval	(2-Sided) 95%; 0 to 19
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value reflects the percentage of participants with unconfirmed complete response unconfirmed (CRu).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Iodine I-131 Tositumomab + CHOP
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	20
	Confidence Interval	(2-Sided) 95%; 4 to 36
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value reflects the percentage of participants with unconfirmed partial response.

2. Secondary Outcome

Title	Number of Participants With the Indicated Confirmed Response (Confirmed Complete Response, Complete Response Unconfirmed, and Partial Response)
Description	A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart. Participants with a confirmed response include those with complete response (CR: complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms), complete response unconfirmed (CRu: CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow), or partial response (PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions). The individual rows for confirmed CR, confirmed CRu, and confirmed PR represent confirmation of the same response. For example, a confirmed CR indicates that a CR was followed by another CR at least 4 weeks later.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population. Only those participants evaluable for response (those with at least one response assessment) were analyzed.

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	22
Confirmed CR	11 44%
Confirmed CRu	2 8%
Confirmed PR	3 12%

3. Secondary Outcome

Title	Duration of Response for All Confirmed Responders (CR + CRu + PR)
Description	Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Complete response unconfirmed (CRu) is defined as CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow. Partial response (PR) is defined as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions. For participants with CR, CRu, or PR, duration of response is defined as the time from the first documented response to the first documented progression.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population. Only those participants (par.) with a confirmed CR, CRu, or PR were analyzed. The number of par. analyzed represents the par. with a confimed CR, CRu, or PR who also had the same response or a better response as confirmation (for example, a par. with an initial CRu and a subsequent CR has been included in the analysis).

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	19
Median (95% Confidence Interval) [Months]	29.8

4. Secondary Outcome

Title	Duration of Response for All Unconfirmed Responders (CR + CRu + PR)
Description	Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Complete response unconfirmed is defined as CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow. Partial response (PR) is defind as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions. Duration of response is defined as the time from the first documented response to the first documented progression.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population. Only those participants with an unconfirmed response (CR, CRu, or PR) were analyzed for duration of response.

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	21
Median (95% Confidence Interval) [Months]	29.8

5. Secondary Outcome

Title	Duration of Response for Unconfirmed Complete Responders
Description	Complete response is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Duration of response is defined as the time from the first documented response to the first documented progression.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population. Only those participants with unconfirmed CR were analyzed.

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	14
Median (95% Confidence Interval) [Months]	31.8

6. Secondary Outcome

Title	Duration of Response for Confirmed Complete Responders
Description	Complete response is the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart. Duration of response is defined as the time from the first documented response to the first documented progression.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population. Only those participants with confirmed CR were analyzed.

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	11
Median (95% Confidence Interval) [Months]	54.0

7. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival is defined as the time from the start of treatment (i.e., the dosimetric dose) to the first documented disease progression or death. Disease progression 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. Individual lesions must have been greater than 2 centimeters (cm) in diameter by radiographic evaluation or greater than 1 cm in diameter by physical examination.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	25
Median (95% Confidence Interval) [Months]	27.6

8. Secondary Outcome

Title	Time to Treatment Failure
Description	Time to treatment failure is defined as the time from the date of the dosimetric dose to the first occurrence of treatment withdrawal, decision to seek additional therapy, study removal, disease progression, alternative therapy, or death.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	25
Median (95% Confidence Interval) [Months]	20.2

9. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAEs are defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; resulted in disability; or was a congenital anomaly. Refer to the general AE/SAE module for a complete list of all AEs and SAEs.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	25
Any AE	25 100%
Any SAE	19 76%

10. Secondary Outcome

Title	Mean Nadir Value for Absolute Neutrophil Count (ANC)
Description	Nadir is defined as the lowest laboratory value recorded following the administration of study medication. ANC is a measure of the number of neutrophil granulocytes present in the blood. Neutrophils are a type of white blood cell that fights infection.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population. Only 24 participants had ANC data available.

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	24
Mean (Standard Deviation) [1000 cells/millimeters cubed (mm^3)]	1.8 (0.93)

11. Secondary Outcome

Title	Mean Nadir Value for Hemoglobin
Description	Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population. Only 24 participants had hemoglobin data available.

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	24
Mean (Standard Deviation) [grams/deciliter (g/dL)]	11.2 (1.51)

12. Secondary Outcome

Title	Mean Nadir Values for Platelets and White Blood Cell (WBC) Count
Description	Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Platelets and WBCs are types of blood cells.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population. Only 24 participants had platelet and WBC data available.

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	24
Platelet count	80.7 (54.18)
WBC count	2.8 (1.30)

13. Secondary Outcome

Title	Time to Nadir for the Indicated Hematology Parameters
Description	Hematology parameters include ANC (calculated), hemoglobin, platelet count, and WBC count. Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Time to nadir is defined as the time from Baseline to the time the lowest value recorded following the therapeutic dose.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population. Only 24 participants had data available.

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	24
ANC	42.9 (5.93)
Hemoglobin	62.1 (41.35)
Platelet count	45.7 (31.51)
WBC count	55.9 (29.43)

14. Secondary Outcome

Title	Time to Recovery From the Indicated Hematology Parameters
Description	Hematology parameters include ANC (calculated), hemoglobin, platelet count, and WBC count. Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Time to recovery to Baseline for the indicated hematologic parameters is defined as the time required for recovery from nadir values to Baseline values.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population. Only 24 participants had data available.

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	24
ANC	49.5
Hemoglobin	84.0
Platelet count	43.5
WBC count	53.0

15. Secondary Outcome

Title	Number of Participants Negative for Human Anti-Murine (Mouse) Antibody (HAMA) at Screening Who Converted to HAMA Positivity or Remained Negative During the Course of the Study
Description	The number of participants who developed human anti-murine (mouse) anibodies (HAMA) after treatment was measured. Conversion to HAMA positivity is relative to Screening (participants were evaluable for HAMA analysis if they were HAMA negative at Screening).
Time Frame	Screening; at Week 7, Week 13, then every 6 months until disease progression or death (up to 143 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	23
Positive	10 40%
Negative	13 52%

16. Secondary Outcome

Title	Number of Participants With an Adverse Event of Cytopenia
Description	The effects of iodine I-131 tositumomab on the growth and function of hematopoietic progenitor cells was measured as the number of participants who had cytopenia. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	25
Thrombocytopenia	3 12%
Pancytopenia	1 4%

17. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from the start of treatment to the date of death from any cause.
Time Frame	Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Outcome Measure Data

Analysis Population Description

ITT-Exposed Population

Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
Measure Participants	25
Median (95% Confidence Interval) [Months]	83.1

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until 4 weeks following the last cycle of CHOP, or until administration of alternative therapy, whichever came first (average of 77.8 months).
Arm/Group Title	Iodine I-131 Tositumomab + CHOP
Arm/Group Description	Participants (par.) with previously untreated mantle cell lymphoma (MCL) were dosed with iodine I-131 tositumomab in two phases, followed by six cycles (21 days per cycle) of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In the first phase (dosimetric dose), par. received an infusion of unlabeled tositumomab (450 milligrams [mg]) over the course of 60 minutes, followed by a 30-minute infusion of tositumomab (35 mg) containing 5 millicurie (mCi) of iodine-131. In the second phase (therapeutic dose), par. received a 60-minute infusion of tositumomab (450 mg), followed by a 30-minute infusion of 35 mg tositumomab containing a participant-specific dose of iodine-131. This dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy).
All Cause Mortality
	Iodine I-131 Tositumomab + CHOP
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Iodine I-131 Tositumomab + CHOP
	Affected / at Risk (%)	# Events
Total	19/25 (76%)
Blood and lymphatic system disorders
Febrile neutropenia	7/25 (28%)
Neutropenia	2/25 (8%)
Lymphadenitis	1/25 (4%)
Thrombocytopenia	1/25 (4%)
Cardiac disorders
Cardiac failure congestive	1/25 (4%)
Cardio-respiratory arrest	1/25 (4%)
Pericarditis	1/25 (4%)
Gastrointestinal disorders
Intussusception	1/25 (4%)
Upper gastrointestinal haemorrhage	1/25 (4%)
General disorders
Pyrexia	1/25 (4%)
Infections and infestations
Herpes zoster	1/25 (4%)
Pneumonia	1/25 (4%)
Sepsis	1/25 (4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	2/25 (8%)
Myelodysplastic syndrome	2/25 (8%)
Endometrial adenocarcinoma	1/25 (4%)
Malignant melanoma	1/25 (4%)
Malignant melanoma in situ	1/25 (4%)
Oesophageal adenocarcinoma	1/25 (4%)
Plasma cell myeloma	1/25 (4%)
Squamous cell carcinoma	1/25 (4%)
Squamous cell carcinoma of skin	1/25 (4%)
Nervous system disorders
Cerebrovascular accident	1/25 (4%)
Peroneal nerve palsy	1/25 (4%)
Syncope	1/25 (4%)
Renal and urinary disorders
Renal failure	1/25 (4%)
Renal failure acute	1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Pleurisy	1/25 (4%)
Pulmonary embolism	1/25 (4%)
Vascular disorders
Orthostatic hypotension	1/25 (4%)
Other (Not Including Serious) Adverse Events
	Iodine I-131 Tositumomab + CHOP
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Anaemia	6/25 (24%)
Neutropenia	3/25 (12%)
Thrombocytopenia	2/25 (8%)
Pancytopenia	1/25 (4%)
Cardiac disorders
Palpitations	2/25 (8%)
Tachycardia	2/25 (8%)
Congenital, familial and genetic disorders
Cardiac septal defect	1/25 (4%)
Ear and labyrinth disorders
Vertigo	2/25 (8%)
Ear discomfort	1/25 (4%)
Endocrine disorders
Hypothyroidism	5/25 (20%)
Goitre	1/25 (4%)
Eye disorders
Conjunctivitis	1/25 (4%)
Dry eye	1/25 (4%)
Halo vision	1/25 (4%)
Vision blurred	1/25 (4%)
Vitreous floaters	1/25 (4%)
Gastrointestinal disorders
Constipation	12/25 (48%)
Nausea	12/25 (48%)
Diarrhoea	9/25 (36%)
Abdominal pain	5/25 (20%)
Stomatitis	4/25 (16%)
Vomiting	4/25 (16%)
Inguinal hernia	3/25 (12%)
Abdominal distension	2/25 (8%)
Dry mouth	2/25 (8%)
Dyspepsia	2/25 (8%)
Oral pain	2/25 (8%)
Abdominal discomfort	1/25 (4%)
Abdominal pain upper	1/25 (4%)
Anorectal discomfort	1/25 (4%)
Dysphagia	1/25 (4%)
Faecal incontinence	1/25 (4%)
Glossitis	1/25 (4%)
Haematochezia	1/25 (4%)
Melaena	1/25 (4%)
Oral discomfort	1/25 (4%)
Retching	1/25 (4%)
General disorders
Fatigue	21/25 (84%)
Pyrexia	9/25 (36%)
Chills	4/25 (16%)
Pain	4/25 (16%)
Chest discomfort	3/25 (12%)
Mucosal inflammation	3/25 (12%)
Asthenia	2/25 (8%)
Early satiety	2/25 (8%)
Local swelling	2/25 (8%)
Oedema peripheral	2/25 (8%)
Chest pain	1/25 (4%)
Gait disturbance	1/25 (4%)
Influenza like illness	1/25 (4%)
Oedema	1/25 (4%)
Infections and infestations
Folliculitis	2/25 (8%)
Nasopharyngitis	2/25 (8%)
Candida infection	1/25 (4%)
Ear infection	1/25 (4%)
Herpes simplex	1/25 (4%)
Herpes zoster	1/25 (4%)
Infection	1/25 (4%)
Oral candidiasis	1/25 (4%)
Pharyngitis	1/25 (4%)
Pseudomonas infection	1/25 (4%)
Staphylococcal infection	1/25 (4%)
Urinary tract infection	1/25 (4%)
Injury, poisoning and procedural complications
Arthropod sting	1/25 (4%)
Contusion	1/25 (4%)
Foot fracture	1/25 (4%)
Laceration	1/25 (4%)
Procedural pain	1/25 (4%)
Tooth fracture	1/25 (4%)
Investigations
Platelets <50000 cells/millimeters cubed (mm^3)	10/25 (40%)
WBC < 2000 cells/mm^3	10/25 (40%)
Absolute neutrophil count (CALC) < 1000 cells/mm^3	6/25 (24%)
Hemoglobin < 8.0 grams per deciliter (g/dL)	3/25 (12%)
Blood pressure increased	2/25 (8%)
Antibody test abnormal	1/25 (4%)
Blood glucose increased	1/25 (4%)
Transaminases increased	1/25 (4%)
Weight decreased	1/25 (4%)
Weight increased	1/25 (4%)
Metabolism and nutrition disorders
Decreased appetite	1/25 (4%)
Dehydration	1/25 (4%)
Hypoglycaemia	1/25 (4%)
Musculoskeletal and connective tissue disorders
Muscle spasms	5/25 (20%)
Pain in extremity	5/25 (20%)
Back pain	4/25 (16%)
Myalgia	4/25 (16%)
Arthralgia	3/25 (12%)
Bone pain	2/25 (8%)
Muscular weakness	2/25 (8%)
Pain in jaw	2/25 (8%)
Joint swelling	1/25 (4%)
Limb discomfort	1/25 (4%)
Musculoskeletal chest pain	1/25 (4%)
Musculoskeletal pain	1/25 (4%)
Nervous system disorders
Neuropathy peripheral	10/25 (40%)
Headache	7/25 (28%)
Dizziness	6/25 (24%)
Dysgeusia	6/25 (24%)
Paraesthesia	3/25 (12%)
Burning sensation	2/25 (8%)
Balance disorder	1/25 (4%)
Dysaesthesia	1/25 (4%)
Hypoaesthesia	1/25 (4%)
Post herpetic neuralgia	1/25 (4%)
Syncope	1/25 (4%)
Psychiatric disorders
Anxiety	1/25 (4%)
Insomnia	1/25 (4%)
Renal and urinary disorders
Pollakiuria	4/25 (16%)
Dysuria	2/25 (8%)
Haematuria	2/25 (8%)
Nocturia	2/25 (8%)
Nephrotic syndrome	1/25 (4%)
Renal failure acute	1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Cough	7/25 (28%)
Dyspnoea	5/25 (20%)
Dyspnoea exertional	5/25 (20%)
Productive cough	5/25 (20%)
Rhinorrhoea	5/25 (20%)
Epistaxis	2/25 (8%)
Nasal congestion	2/25 (8%)
Oropharyngeal pain	2/25 (8%)
Upper respiratory tract congestion	2/25 (8%)
Asthma	1/25 (4%)
Respiratory tract congestion	1/25 (4%)
Sputum discoloured	1/25 (4%)
Upper-airway cough syndrome	1/25 (4%)
Upper respiratory tract infection	6/25 (24%)
Skin and subcutaneous tissue disorders
Rash	6/25 (24%)
Erythema	3/25 (12%)
Night sweats	2/25 (8%)
Pruritus	2/25 (8%)
Rash pruritic	2/25 (8%)
Acne	1/25 (4%)
Alopecia	1/25 (4%)
Rosacea	1/25 (4%)
Urticaria	1/25 (4%)
Vascular disorders
Hypotension	4/25 (16%)
Phlebitis	1/25 (4%)
Thrombophlebitis superficial	1/25 (4%)

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.