Lymphoma, Non-Hodgkin
Conditions
Keywords
Radioimmunotherapy, Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody, Tositumomab and Iodine I 131 Tositumomab, non-Hodgkin's Lymphoma, Bexxar
Brief summary
This is a single-arm, single-institution, phase II study of Iodine-131 Anti-B1 Antibody for patients with previously untreated, advanced-stage (stage III or IV) low-grade non-Hodgkin's B-cell lymphoma. A total of 75-80 patients will be enrolled. Patients will undergo two phases of the study. In the first phase, termed the dosimetric dose, patients will receive an infusion of unlabeled Anti-B1 Antibody (450 mg) over 70 minutes (including a 10-minute flush) immediately followed by a 30-minute infusion (including a 10-minute flush) of Anti-B1 Antibody (35 mg) which has been trace-labeled with 5 mCi of Iodine-131. Whole body gamma camera scans will be obtained 5 to 8 times between Days 0 and 7 following the dosimetric dose. Using the dosimetric data from 3 imaging timepoints (the imaging timepoints to be used in decreasing order of preference depending on availability of data are Days 0, 3, and 7; Days 0, 4, and 7; Days 0, 3 and 6; Days 0, 4, and 6; Days 0, 2, and 7; and Days 0, 2, and 6), a patient-specific dose of Iodine- 131 to deliver the desired total body dose of radiotherapy will be calculated. In the second phase, termed the therapeutic dose, patients will receive a 70-minute infusion (including a 10-minute flush) of unlabeled Anti-B1 Antibody (450 mg) immediately followed by a 30-minute infusion (including a 10-minute flush) of Anti-B1 Antibody (35 mg) labeled with the patient-specific dose of Iodine-131 to deliver a whole body dose of 75 cGy. Patients who are obese will be dosed based upon 137% of their calculated lean body mass. Patients will be treated with either saturated solution potassium iodide (SSKI), Lugol's solution, or potassium iodide tablets starting at least 24 hours prior to the first infusion of the Iodine-131 Anti-B1 Antibody (i.e., dosimetric dose) and continuing for 14 days following the last infusion of Iodine-131 Anti-B1 Antibody (i.e., therapeutic dose). The primary endpoint of the study is the determination of the response rate with Iodine-131 Anti-B1 Antibody in previously untreated patients with low-grade non-Hodgkin's lymphoma (NHL). The secondary endpoints include duration of response, safety, radiation dosimetry, and the predictive value of detection of the presence or absence minimal residual disease by molecular techniques on response duration.
Interventions
BIOLOGICALTositumomab and Iodine I 131 Tositumomab (Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody)
Dosimetric Dose: 450 mg of Anti-B1 Antibody infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by 5 mCi (35 mg) of Iodine-131 Anti-B1 Antibody infused over 30 minutes (inclusive of a 10-minute flush). Therapeutic Dose: Seven to 14 days after the dosimetric dose, 450 mg of Anti-B1 Antibody infused over 70 minutes (inclusive of a 10-minute flush), immediately followed by the patient-specific milliCurie activity (35 mg) of Iodine-131 Anti-B1 Antibody to deliver a total body dose (TBD) of 75 cGy infused over 30 minutes (inclusive of a 10-minute flush). Obese patients were dosed based upon 137% of their calculated lean body mass.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a histologically confirmed diagnosis of lowgrade non-Hodgkin's B-cell lymphoma. The following low-grade histologies are included: small lymphocytic (with or without plasmacytoid differentiation); follicular, small cleaved; follicular, mixed small cleaved and follicular large cell (less than 50% large cell component); and monocytoid B-cell lymphoma. * 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 (\>50% of tumor cells are positive) or evidence of CD20 positivity by flow cytometry (\>50% of tumor cells are positive) are acceptable evidence of CD20 positivity. Testing of tumor tissue from any time in the course of the patient's disease is acceptable. * Patients must have Ann Arbor stage III or IV extent of disease after complete staging. * Patients must not have had any previous treatment for low-grade lymphoma including chemotherapy or radiation. They may be newly diagnosed or observed without treatment after diagnosis. Symptomatic and asymptomatic patients will be eligible. * Patients must have a performance status of at least 60% on the Karnofsky Scale and an anticipated survival of at least 3 months. * Patients must have an absolute neutrophil count (ANC) \>1500 cells/mm3 and a platelet count \>100,000 cells/mm3 within 14 days of study entry. 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 x upper limit of normal \[ULN\]) and hepatic function (defined as total bilirubin \<1.5 x ULN and aspartate transaminase \[AST\] \<5 x ULN) within 14 days of study entry. * Patients must have bi-dimensionally measurable disease. At least one lesion must be ≥2 x 2 cm (by computed tomography \[CT\] scan). * Patients must be at least 18 years of age. * Patients must give written informed consent and sign an IRB- approved informed consent form prior to study entry.
Exclusion criteria
* Patients 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 intratrabecular space involved exceeds 10% on a unilateral biopsy. The mean of bilateral biopsies must be no more than 25%. * Patients with evidence of active infection requiring intravenous (IV) antibiotics at the time of study entry. * Patients with New York Heart Association class III or IV heart disease or other serious illness that would preclude evaluation. * Patients with active obstructive hydronephrosis. * 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 with known brain or leptomeningeal metastases. * Patients who are pregnant or nursing. Patients of childbearing potential must undergo a pregnancy test within 7 days of study entry and radiolabeled antibody is not to be administered until a negative result is obtained. Males and females must agree to use effective contraception for 6 months following the radioimmunotherapy. * Patients with previous allergic reactions to iodine. This does not include reacting to IV iodine-containing contrast materials. * Patients who were previously given any monoclonal or polyclonal antibodies of any non-human species for either diagnostic or therapeutic purposes. This includes engineered chimeric and humanized antibodies. * Patients who are concurrently receiving either approved or nonapproved (through another protocol) anti-cancer drugs or biologics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Confirmed Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | From Study Day 0 (start of treatment) up to 12 years (long-term follow up) | Confirmed response required CR, CCR, or PR, which were confirmed by 2 separate response evaluations \>=4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions. |
| Number of Participants With Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), or Partial Response (PR) | From Study Day 0 (start of treatment) up to 12 years (long-term follow up) | CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions. |
| Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) | From Study Day 0 (start of treatment) up to 12 years (long-term follow up) | Responses were confirmed by two separate response evaluations at least 4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions. |
| Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) | From Study Day 0 (start of treatment) up to 12 years (long-term follow up) | CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Were Polymerase Chain Reaction (PCR)-Positive at Baseline With Bone Marrow Conversion to a Status of PCR Positive and Negative Any Time After Treatment | Baseline and up to 12 years (long-term follow up) | PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent. |
| Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment | Baseline and up to 12 years (long-term follow up) | PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent. |
| Progression-free Survival (PFS) Based on Participants' Baseline PCR Status | Baseline and up to 12 years (long-term follow up) | PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent. PFS is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death. |
| Initial Half-life (t1/2alpha) | 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7) | t1/2 alpha is the estimated initial or alpha phase half-life in a two-compartmental pharmacokinetic model. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half. |
| Terminal Half-life (t1/2beta) | 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7) | t1/2 beta is the estimated terminal or beta phase half-life in a two-compartmental pharmacokinetic model. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half. |
| Area Under the Curve (AUC) at 0 to 120 Hours and 0 to Infinity Hours | 0-120 hours and 0-infinity hours from the dosimetric dose (given only on Day 0) and 0-120 hours and 0-infinity hours from the therapeutic dose (given only on Day 7) | Area under the concentration-time curve for I-131 tositumomab from time 0 to 120 hours and time 0 to infinity hours (extrapolated) after the end of the dosimetric dose infusion was measured. Unit: %ID\*h/ml, where %ID/ml is the percentage of the injected dose per milliliter of blood. AUC measures how much drug is in the system over time after infusion. |
| Clearance Values | 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7) | Clearance of I-131 tositumomab after intravenous administration was measured. The clearance of a drug measures the rate at which the drug is removed from the body after the dose. |
| Maximum Concentration (Cmax) Values | 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7) | Cmax is the maximum observed I-131 tositumomab concentration from time zero (end of the dosimetric dose infusion) to 120 hours after the end of the infusion. Unit: %ID/ml, where %ID/ml is the percentage of the injected dose per milliliter of blood. Cmax is the highest drug concentration in the blood after infusion. |
| Volume of Distribution at Infusion Time 0 (Vd0) and Steady State (Vdss) | 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7) | Volume of distribution at the start of infusion and at steady state of I-131 tositumomab. The volume of distribution measures how much the drug spreads through the body after the dose. Steady state is defined as that state at which the overall intake of a drug is fairly in dynamic equilibrium with its elimination. |
| Total Body Effective Half-life (EHL) | 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7) | Total body EHL is the time required for a radioactive element in the body to be diminished by 50% as a result of radioactive decay and biologic elimination. The EHL is equal to the product of the biologic half-life (BHL) and the radioactive half-life (RHL) divided by the sum of the BHL and the RHL: EHL=(BHL \* RHL)/(BHL + RHL). BHL is the time it takes for a drug to lose half of its pharmacologic, physiologic, or radiologic activity. RHL is the time taken for half of the radioactive nuclei to decay. |
| The Estimated Value Represents the Percentage of Participants With a PR | From Study Day 0 (start of treatment) up to 12 years (long-term follow up) | Duration of response (CR, CCR, or PR) is defined as the time from the first documented response to the first documented progression. Progressive Disease (PD) is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. |
| Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) | From Baseline up to 12 years from the start of treatment (long-term follow up) | An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. A fatal SAE is a medical event that results in death. |
| Number of Participants Evaluable and Not Evaluable for Human Anti-Murine Antibodies (HAMA) | From Baseline up to 2 years from the start of treatment | Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA. |
| Number of Participants With Conversion to HAMA Positivity Any Time During the Study From Baseline | From Baseline up to 2 years from the start of treatment | Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment. |
| Time to HAMA Positivity From the First Dosimetric Dose | From Baseline up to 2 years from the start of treatment | Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment. |
| Number of Participants With Elevated, Low, and Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline | Baseline | TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were considered to have normal, high, or low TSH levels per the standard TSH ranges of the testing laboratory. |
| Participants With Elevated TSH Levels at Baseline With Post Baseline TSH Levels of Low/Normal and Elevated | Baseline and up to 12 years (long-term follow up) | TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were considered to have normal, high, or low TSH levels per the standard TSH ranges of the testing laboratory. |
| Time to Elevated TSH Post Baseline for Participants Who Had Low or Normal TSH Levels at Baseline and Elevated Levels Post Baseline | Baseline and up to 12 years from the start of treatment | TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were categorized to have elevated or normal/low TSH values per the standard TSH ranges of the testing laboratory. |
| Number of Participants With the Adverse Event (AEs) of Hypothyroidism | Baseline and up to 12 years from the start of treatment | Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication. An AE is defined as any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered to be related to the medical treatment or procedure, that occurs during the course of the study. |
| Number of Participants With Low or Normal Baseline TSH Levels That Developed Hypothyroidism | Baseline and up to 12 years from the start of treatment | Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication. |
| Number of Participants Who Received Thyroid Medication After Treatment | From Study Day 0 (start of treatment) up to 12 years (long-term follow up) | Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication. |
| Normal Organ Dosimetry for the Indicated Organs | 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7) | Organ dosimetry was performed in participants using the kidneys, liver, lungs, spleen, red marrow, urinary bladder, and the remainder of the body as source organs. Organ doses and Iodine I-131 Anti-B1 Antibody biodistribution were comparable across the three Anti-B1 Antibody manufacturers. Gamma camera images of participants were used to calculate the amount of radiation that accumulated in the target tumor and normal organs (tumor/organ dosimetry). For the spleen (corrected) category, participant-specific corrections were made to account for individual spleen size. |
| Overall Survival | From Study Day 0 (start of treatment) up to 12 years (long-term follow up) | Overall survival is defined as the time from the treatment start date to the date of death from any cause. |
| Time to Progression of Disease or Death (Progression-free Survival) | From Study Day 0 (start of treatment) up to 12 years (long-term follow up) | Time to progression is defined as the time from the treatment start date to the first documented progression or death. Progressive Disease is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. |
| Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study | Baseline and up to 12 years (long-term follow up) | The Ann Arbor staging system of lymphomas is used to summarize the extent of the cancer's spread. Stages are classified by Roman numerals I (less spread) to IV (more spread). If the following symptoms (called B-symptoms) are present, a B classification is added to the stage: night sweats, intermittant fever, and weight loss. B-symptoms indicate the presence of systemic symptoms. The presence or absence of B-symptoms has prognostic significance and is reflected in the staging of these lymphomas. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tositumomab and Iodine I-131 Tositumomab Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) over 70 minutes, followed immediately by 5 millicurie (mCi) iodine I-131 tositumomab (contained in 35 mg tositumomab) infused over 30 minutes. Therapeutic dose (administered only once 7 to 14 days after the dosimetric dose): 450 mg unlabeled tositumomab administered IV over 70 minutes, followed immediately by iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV infused over 30 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy). | 76 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Did Not Receive Study Medications | 1 |
| Overall Study | Lost to Follow-up | 9 |
| Overall Study | Non-compliance | 8 |
| Overall Study | Progressive Disease | 10 |
Baseline characteristics
| Characteristic | Tositumomab and Iodine I-131 Tositumomab |
|---|---|
| Age, Continuous | 48.1 Years STANDARD_DEVIATION 9.9 |
| Gender Female | 35 Participants |
| Gender Male | 41 Participants |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants |
| Race/Ethnicity, Customized White | 74 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 76 / 76 |
| serious Total, serious adverse events | 19 / 76 |
Outcome results
Primary
Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR)
CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Time frame: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) | CR | 56 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) | CCR | 3 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) | CR+CCR | 59 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) | PR | 15 participants |
95% CI: [64, 84]
95% CI: [0, 8]
95% CI: [68, 87]
95% CI: [11, 29]
Primary
Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR)
Responses were confirmed by two separate response evaluations at least 4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Time frame: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Population: ITT-Exposed Population. Only participants evaluable for confirmed response (R) were assessed. R had to be confirmed by a consecutive R that was the same or better \>=4 weeks apart. Each individual confirmed R category only counts the R confirmed by the exact same R; therefore, not all possible combinations are represented in the table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) | CR | 53 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) | CCR | 2 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) | CR+CCR | 57 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Confirmed Complete Response (CR, CCR, and CR+CCR) and Partial Response (PR) | PR | 13 participants |
95% CI: [59, 80]
95% CI: [0, 6]
95% CI: [65, 85]
95% CI: [9, 26]
Primary
Number of Participants With Confirmed Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR)
Confirmed response required CR, CCR, or PR, which were confirmed by 2 separate response evaluations \>=4 weeks apart. CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Time frame: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Population: ITT-Exposed Population: all participants who were enrolled in the study and received at least one dose of study drug. Only participants evaluable for confirmed response were assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Confirmed Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), and Partial Response (PR) | 72 participants |
95% CI: [90, 100]
Primary
Number of Participants With Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), or Partial Response (PR)
CR: Complete resolution of all disease-related radiological abnormalities and disappearance of all signs and symptoms related to the disease. CCR: Complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.
Time frame: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Response, Including Participants With Complete Response (CR), Clinical Complete Response (CCR), or Partial Response (PR) | 74 participants |
95% CI: [94, 100]
Secondary
Area Under the Curve (AUC) at 0 to 120 Hours and 0 to Infinity Hours
Area under the concentration-time curve for I-131 tositumomab from time 0 to 120 hours and time 0 to infinity hours (extrapolated) after the end of the dosimetric dose infusion was measured. Unit: %ID\*h/ml, where %ID/ml is the percentage of the injected dose per milliliter of blood. AUC measures how much drug is in the system over time after infusion.
Time frame: 0-120 hours and 0-infinity hours from the dosimetric dose (given only on Day 0) and 0-120 hours and 0-infinity hours from the therapeutic dose (given only on Day 7)
Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to 120 Hours and 0 to Infinity Hours | AUC(0-infinity) | 1.43 %ID*h/ml | Standard Deviation 0.41 |
| Tositumomab and Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to 120 Hours and 0 to Infinity Hours | AUC(0-120) | 1.03 %ID*h/ml | Standard Deviation 0.26 |
Secondary
Clearance Values
Clearance of I-131 tositumomab after intravenous administration was measured. The clearance of a drug measures the rate at which the drug is removed from the body after the dose.
Time frame: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Clearance Values | 77.34 Milliliters per hour (ml/hr) | Standard Deviation 28.73 |
Secondary
Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment
PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent.
Time frame: Baseline and up to 12 years (long-term follow up)
Population: ITT-Exposed Population. Only those participants who were PCR positive at Baseline and converted to a status of PCR negative were assessed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment | All responders (CR+CCR+PR), n=38 | 59.5 months |
| Tositumomab and Iodine I-131 Tositumomab | Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment | Complete responders (CR+CCR), n=30 | 98.2 months |
| Tositumomab and Iodine I-131 Tositumomab | Duration of Response (the Time From the First Documented Response to the First Documented Progression) for Participants Who Were PCR Positive at Baseline and Converted to PCR Negative Status After Treatment | Partial responders, n=8 | 6.9 months |
Secondary
Initial Half-life (t1/2alpha)
t1/2 alpha is the estimated initial or alpha phase half-life in a two-compartmental pharmacokinetic model. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half.
Time frame: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Initial Half-life (t1/2alpha) | 3.85 hours | Standard Deviation 3.33 |
Secondary
Maximum Concentration (Cmax) Values
Cmax is the maximum observed I-131 tositumomab concentration from time zero (end of the dosimetric dose infusion) to 120 hours after the end of the infusion. Unit: %ID/ml, where %ID/ml is the percentage of the injected dose per milliliter of blood. Cmax is the highest drug concentration in the blood after infusion.
Time frame: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Maximum Concentration (Cmax) Values | 0.020 %ID/ml | Standard Deviation 0.005 |
Secondary
Normal Organ Dosimetry for the Indicated Organs
Organ dosimetry was performed in participants using the kidneys, liver, lungs, spleen, red marrow, urinary bladder, and the remainder of the body as source organs. Organ doses and Iodine I-131 Anti-B1 Antibody biodistribution were comparable across the three Anti-B1 Antibody manufacturers. Gamma camera images of participants were used to calculate the amount of radiation that accumulated in the target tumor and normal organs (tumor/organ dosimetry). For the spleen (corrected) category, participant-specific corrections were made to account for individual spleen size.
Time frame: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Population: ITT-Exposed Population. Only those participants who had available gamma camera images for the indicated organs were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Normal Organ Dosimetry for the Indicated Organs | Liver, n=76 | 221.69 cGy/75 cGy total body dose (TBD) | Standard Deviation 43.721 |
| Tositumomab and Iodine I-131 Tositumomab | Normal Organ Dosimetry for the Indicated Organs | Kidney, n=75 | 637.35 cGy/75 cGy total body dose (TBD) | Standard Deviation 129.36 |
| Tositumomab and Iodine I-131 Tositumomab | Normal Organ Dosimetry for the Indicated Organs | Spleen, n=74 | 835.92 cGy/75 cGy total body dose (TBD) | Standard Deviation 358.61 |
| Tositumomab and Iodine I-131 Tositumomab | Normal Organ Dosimetry for the Indicated Organs | Spleen (corrected), n=72 | 393.38 cGy/75 cGy total body dose (TBD) | Standard Deviation 120.602 |
| Tositumomab and Iodine I-131 Tositumomab | Normal Organ Dosimetry for the Indicated Organs | Blood, n=76 | 364.60 cGy/75 cGy total body dose (TBD) | Standard Deviation 64.608 |
| Tositumomab and Iodine I-131 Tositumomab | Normal Organ Dosimetry for the Indicated Organs | Red Bone Marrow, n=41 | 105.57 cGy/75 cGy total body dose (TBD) | Standard Deviation 10.342 |
| Tositumomab and Iodine I-131 Tositumomab | Normal Organ Dosimetry for the Indicated Organs | Thyroid, n=76 | 59.50 cGy/75 cGy total body dose (TBD) | Standard Deviation 3.17 |
| Tositumomab and Iodine I-131 Tositumomab | Normal Organ Dosimetry for the Indicated Organs | Urine Bladder Wall, n=76 | 214.28 cGy/75 cGy total body dose (TBD) | Standard Deviation 38.563 |
| Tositumomab and Iodine I-131 Tositumomab | Normal Organ Dosimetry for the Indicated Organs | Gall Bladder Wall, n=76 | 89.39 cGy/75 cGy total body dose (TBD) | Standard Deviation 3.929 |
| Tositumomab and Iodine I-131 Tositumomab | Normal Organ Dosimetry for the Indicated Organs | Tumor, n=61 | 835.86 cGy/75 cGy total body dose (TBD) | Standard Deviation 499.817 |
Secondary
Number of Participants Evaluable and Not Evaluable for Human Anti-Murine Antibodies (HAMA)
Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA.
Time frame: From Baseline up to 2 years from the start of treatment
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants Evaluable and Not Evaluable for Human Anti-Murine Antibodies (HAMA) | Evaluable | 73 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants Evaluable and Not Evaluable for Human Anti-Murine Antibodies (HAMA) | Not evaluable | 3 participants |
Secondary
Number of Participants Who Received Thyroid Medication After Treatment
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication.
Time frame: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants Who Received Thyroid Medication After Treatment | 11 participants |
Secondary
Number of Participants Who Were Polymerase Chain Reaction (PCR)-Positive at Baseline With Bone Marrow Conversion to a Status of PCR Positive and Negative Any Time After Treatment
PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent.
Time frame: Baseline and up to 12 years (long-term follow up)
Population: ITT-Exposed Population. Only those participants with a PCR-positive status at Baseline were assessed. One participant had a Baseline measurement but no post Baseline measure, and was thus not assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants Who Were Polymerase Chain Reaction (PCR)-Positive at Baseline With Bone Marrow Conversion to a Status of PCR Positive and Negative Any Time After Treatment | PCR Positive after treatment | 1 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants Who Were Polymerase Chain Reaction (PCR)-Positive at Baseline With Bone Marrow Conversion to a Status of PCR Positive and Negative Any Time After Treatment | PCR Negative after treatment | 38 participants |
Secondary
Number of Participants With Conversion to HAMA Positivity Any Time During the Study From Baseline
Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment.
Time frame: From Baseline up to 2 years from the start of treatment
Population: ITT-Exposed Population. Only those participants who were evaluable for HAMA were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Conversion to HAMA Positivity Any Time During the Study From Baseline | Positive | 51 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Conversion to HAMA Positivity Any Time During the Study From Baseline | Negative | 22 participants |
Secondary
Number of Participants With Elevated, Low, and Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline
TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were considered to have normal, high, or low TSH levels per the standard TSH ranges of the testing laboratory.
Time frame: Baseline
Population: ITT-Exposed Population. Only those participants for whom TSH levels were recorded at Baseline were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Elevated, Low, and Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline | Elevated TSH at Baseline | 4 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Elevated, Low, and Normal Thyroid Stimulating Hormone (TSH) Levels at Baseline | Low/Normal TSH at Baseline | 69 participants |
Secondary
Number of Participants With Low or Normal Baseline TSH Levels That Developed Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication.
Time frame: Baseline and up to 12 years from the start of treatment
Population: ITT-Exposed Population. Only those participants who had low or normal Baseline TSH levels were assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Low or Normal Baseline TSH Levels That Developed Hypothyroidism | 6 participants |
Secondary
Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study
The Ann Arbor staging system of lymphomas is used to summarize the extent of the cancer's spread. Stages are classified by Roman numerals I (less spread) to IV (more spread). If the following symptoms (called B-symptoms) are present, a B classification is added to the stage: night sweats, intermittant fever, and weight loss. B-symptoms indicate the presence of systemic symptoms. The presence or absence of B-symptoms has prognostic significance and is reflected in the staging of these lymphomas.
Time frame: Baseline and up to 12 years (long-term follow up)
Population: ITT-Exposed Population. Only those participants who experienced any B-symptom at Baseline were assessed. Not all participants experienced all B-symptoms at Baseline; thus, the number of participants analyzed represents all participants who experienced at least one B-symptom.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study | Night sweats, n=8 | 8 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study | Intermittant fever, n=3 | 3 participants |
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With Resolution of All Baseline B-symptoms by the End of the Study | Weight loss, n=4 | 4 participants |
Secondary
Number of Participants With the Adverse Event (AEs) of Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone and is defined as either developing elevated TSH levels or initiating thyroid medication. An AE is defined as any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered to be related to the medical treatment or procedure, that occurs during the course of the study.
Time frame: Baseline and up to 12 years from the start of treatment
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With the Adverse Event (AEs) of Hypothyroidism | 8 participants |
Secondary
Number of Participants With the Indicated Fatal Serious Adverse Events (SAE)
An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. A fatal SAE is a medical event that results in death.
Time frame: From Baseline up to 12 years from the start of treatment (long-term follow up)
Population: ITT-Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) | 1 participants |
Secondary
Overall Survival
Overall survival is defined as the time from the treatment start date to the date of death from any cause.
Time frame: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Population: ITT-Exposed Population. Only those participants who died during the study due to any cause were assessed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Overall Survival | NA months |
Secondary
Participants With Elevated TSH Levels at Baseline With Post Baseline TSH Levels of Low/Normal and Elevated
TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were considered to have normal, high, or low TSH levels per the standard TSH ranges of the testing laboratory.
Time frame: Baseline and up to 12 years (long-term follow up)
Population: ITT-Exposed Population. Only participants with elevated TSH levels at Baseline were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Participants With Elevated TSH Levels at Baseline With Post Baseline TSH Levels of Low/Normal and Elevated | Low/Normal TSH Post Baseline | 61 participants |
| Tositumomab and Iodine I-131 Tositumomab | Participants With Elevated TSH Levels at Baseline With Post Baseline TSH Levels of Low/Normal and Elevated | Elevated TSH Post Baseline | 8 participants |
Secondary
Progression-free Survival (PFS) Based on Participants' Baseline PCR Status
PCR is a scientific technique in molecular biology to amplify a single copy or a few copies of a piece of deoxyribonucleic acid (DNA) across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. Applications of PCR technique include: selective DNA isolation, amplification and quantification of DNA, and the diagnosis of diseases. PCR positive: interchromosomal translocation t(14;18) is present. PCR negative: t(14;18) is absent. PFS is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death.
Time frame: Baseline and up to 12 years (long-term follow up)
Population: ITT-Exposed Population. Only those participants with a PCR status taken at Baseline were evaluated for PFS.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Progression-free Survival (PFS) Based on Participants' Baseline PCR Status | PCR-negative participants, n=33 | 130.8 months |
| Tositumomab and Iodine I-131 Tositumomab | Progression-free Survival (PFS) Based on Participants' Baseline PCR Status | PCR-positive participants, n=40 | 48.8 months |
Secondary
Terminal Half-life (t1/2beta)
t1/2 beta is the estimated terminal or beta phase half-life in a two-compartmental pharmacokinetic model. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half.
Time frame: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Terminal Half-life (t1/2beta) | 64.57 hours | Standard Deviation 16.23 |
Secondary
The Estimated Value Represents the Percentage of Participants With a PR
Duration of response (CR, CCR, or PR) is defined as the time from the first documented response to the first documented progression. Progressive Disease (PD) is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion.
Time frame: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Population: ITT-Exposed Population. Only participants who experienced confirmed CR, CCR, or PR with PD were assessed. Response (R) had to be confirmed by a consecutive R that was the same or better \>=4 weeks apart. Each individual confirmed R category only counts the R confirmed by the exact same R; therefore, not all possible combinations are represented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | The Estimated Value Represents the Percentage of Participants With a PR | Confirmed CR+CCR+PR, n=45 | 98.0 months |
| Tositumomab and Iodine I-131 Tositumomab | The Estimated Value Represents the Percentage of Participants With a PR | Confirmed CR+CCR, n=30 | 129.2 months |
| Tositumomab and Iodine I-131 Tositumomab | The Estimated Value Represents the Percentage of Participants With a PR | Confirmed PR, n=13 | 6.9 months |
| Tositumomab and Iodine I-131 Tositumomab | The Estimated Value Represents the Percentage of Participants With a PR | Confirmed CR, n=27 | 130.7 months |
| Tositumomab and Iodine I-131 Tositumomab | The Estimated Value Represents the Percentage of Participants With a PR | Confirmed CCR, n=2 | 11.8 months |
Secondary
Time to Elevated TSH Post Baseline for Participants Who Had Low or Normal TSH Levels at Baseline and Elevated Levels Post Baseline
TSH is a hormone that stimulates the thyroid gland to produce thyroxine (T4) and then triiodothyronine (T3), which stimulates the metabolism of almost every tissue in the body. Participants were categorized to have elevated or normal/low TSH values per the standard TSH ranges of the testing laboratory.
Time frame: Baseline and up to 12 years from the start of treatment
Population: ITT-Exposed Population. Only those participants who had low or normal TSH levels at Baseline and elevated levels post Baseline were assessed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Time to Elevated TSH Post Baseline for Participants Who Had Low or Normal TSH Levels at Baseline and Elevated Levels Post Baseline | 33.2 months |
Secondary
Time to HAMA Positivity From the First Dosimetric Dose
Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants were evaluated to determine whether they developed an immune response to study treatment, as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I-131 tositumomab. A positive HAMA value indicates that the participant developed HAMA above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of HAMA. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment.
Time frame: From Baseline up to 2 years from the start of treatment
Population: ITT-Exposed Population. Only those participants who converted from being negative for HAMA at Baseline to being positive for HAMA any time following treatment were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Time to HAMA Positivity From the First Dosimetric Dose | 93.5 days | Standard Deviation 152.6 |
Secondary
Time to Progression of Disease or Death (Progression-free Survival)
Time to progression is defined as the time from the treatment start date to the first documented progression or death. Progressive Disease is defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion.
Time frame: From Study Day 0 (start of treatment) up to 12 years (long-term follow up)
Population: ITT-Exposed Population. Only those participants who experienced disease progression or died were assessed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Time to Progression of Disease or Death (Progression-free Survival) | 74.3 months |
Secondary
Total Body Effective Half-life (EHL)
Total body EHL is the time required for a radioactive element in the body to be diminished by 50% as a result of radioactive decay and biologic elimination. The EHL is equal to the product of the biologic half-life (BHL) and the radioactive half-life (RHL) divided by the sum of the BHL and the RHL: EHL=(BHL \* RHL)/(BHL + RHL). BHL is the time it takes for a drug to lose half of its pharmacologic, physiologic, or radiologic activity. RHL is the time taken for half of the radioactive nuclei to decay.
Time frame: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Population: ITT-Exposed Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Total Body Effective Half-life (EHL) | 63.6 hours | Standard Deviation 8.44 |
Secondary
Volume of Distribution at Infusion Time 0 (Vd0) and Steady State (Vdss)
Volume of distribution at the start of infusion and at steady state of I-131 tositumomab. The volume of distribution measures how much the drug spreads through the body after the dose. Steady state is defined as that state at which the overall intake of a drug is fairly in dynamic equilibrium with its elimination.
Time frame: 0-120 hours from the dosimetric dose (given only on Day 0) and 0-120 hours from the therapeutic dose (given only on Day 7)
Population: ITT-Exposed Population. Only those participants for whom pharmacokinetic blood samples were collected at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tositumomab and Iodine I-131 Tositumomab | Volume of Distribution at Infusion Time 0 (Vd0) and Steady State (Vdss) | Vd0 | 5297 milliliters (ml) | Standard Deviation 1123 |
| Tositumomab and Iodine I-131 Tositumomab | Volume of Distribution at Infusion Time 0 (Vd0) and Steady State (Vdss) | Vdss | 6710 milliliters (ml) | Standard Deviation 1700 |