Lymphoma, Follicular
Conditions
Keywords
Bexxar, tositumomab and iodine I 131 tositumomab therapeutic regiment, fission, Non-Hodgkin's lymphoma, Iodine I 131 Tositumomab, pharmacokinetics, tellurium
Brief summary
Patients will receive a standard 5 mCi dosimetric dose of fission-derived Iodine I 131 Tositumomab. Pharmacokinetic data for the primary endpoint analysis will be derived from testing done on blood samples drawn at 12 timepoints over the first 7 days following administration of the dosimetric dose. Whole body gamma camera images will be obtained on six days following the dosimetric dose. Organ and tumor dosimetry data will be generated from gamma camera counts of specific organs and tumor. All scans will be examined by an independent review panel to evaluate biodistribution of the radionuclide. Using the dosimetric data from three of the six imaging time points and the patient's weight, a patient-specific activity (mCi) of Iodine-131 will be calculated to deliver the desired total body dose of radiation (75 cGy). Patients will receive an infusion of unlabeled Tositumomab (450 mg) immediately followed by an infusion of the patient specific dose of tellurium-derived Iodine I 131 Tositumomab (35 mg) to deliver a total body dose (TBD) of 75 cGy. Patients will be followed closely obtaining safety information during the post-treatment period, and for response and safety at 3,6,and 12 months during the first year, annually thereafter up to five years, and annually for additional safety and outcomes information up to 10 years.
Interventions
BIOLOGICALFollicular Lymphoma
For subjects with previously untreated or relapsed follicular or transformed follicular non-Hodgkin's
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
1. At least 18 years of age 2. A histologically confirmed diagnosis of the following: Follicular lymphoma, Grade 1, 2, or 3 or diffuse large cell lymphoma concurrent with or following the diagnosis of follicular lymphoma (World Health Organization/Revised European-American Lymphoma \[WHO/REAL\] classification). International Working Formulation histological equivalents included: Follicular, small-cleaved; Follicular, mixed small-cleaved and large-cell; Follicular large-cell; or Transformed diffuse large-cell lymphoma following or concurrent with a diagnosis of follicular lymphoma. 3. Stage III or IV disease at the time of study entry (based on Ann Arbor Staging Classification) 4. Previously untreated or recurrent lymphoma after no more than 4 prior qualifying therapy regimens; steroids alone, as treatment for lymphoma, not considered a treatment regimen 5. Performance status of at least 70% on the Karnofsky Performance Scale and an anticipated survival of at least 3 months. 6. Bi dimensionally measurable disease with at least one lesion measuring greater than or equal to 2.0 cm x 2.0 cm (greater than or equal to 4.0 cm2) by computed tomography (CT) scan 7. Absolute B lymphocyte count (as determined by CD19 reactivity \[flow cytometric determination of CD19+ B lymphocyte count\]) of 30 to 350 cell/mm3 within 21 days prior to study enrollment 8. Absolute neutrophil count greater than or equal to 1500 cells/mm3; platelet count greater than or equal to 150,000/mm3; and hemoglobin greater than or equal to 10 g/dL within 21 days prior to study enrollment; blood products and/or growth factors not taken within 4 weeks prior to blood draw 9. 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 21 days of study enrollment 10. HAMA negative within 21 days prior to study enrollment 11. Signed IRB approved consent form prior to any study-specific procedures being implemented
Exclusion criteria
1. Greater than 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically within 90 days of study enrollment; a unilateral bone marrow biopsy was adequate; marrow core was greater than or equal to 2.0 cm in length 2. Prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for NHL within 28 days prior to study enrollment; subjects receiving low doses of steroids for non neoplastic disease acceptable to enter this study (Low dose steroids was defined as less than or equal to 10 mg of prednisone or equivalent per day.) 3. Prior rituximab therapy within 120 days prior to study enrollment 4. Prior radioimmunotherapy 5. Prior splenectomy 6. Splenomegaly defined as spleen mass greater than 700 grams, where splenic mass was defined as follows: Spleen mass = л(X x Y x Z)/6 Where X and Y are the greatest perpendicular diameters in cm on any single CT scan slice, and Z is the number of CT scan slices upon which the spleen is visible times the slice thickness in cm 7. Bulky disease as defined as any uni-dimensional measurement of lymphomatous mass exceeding 7 cm 8. Prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the subject had a generally accepted risk of recurrence less than 20% 9. Central nervous system involvement by lymphoma 10. Evidence of active infection requiring IV antibiotics at the time of study enrollment 11. Known human immunodeficiency virus (HIV) infection 12. New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation. 13. Active obstructive hydronephrosis 14. Evidence of clinically significant ascites or pleural effusion observed on screening physical examination or baseline CT scan 15. Prior myeloablative therapy 16. History of failed stem cell collection 17. Pregnant or nursing subjects (Subjects of childbearing potential had to have a negative serum pregnancy test within 21 days of study enrollment. Males and females of childbearing age had to agree to use effective contraception for up to 12 months after the radioimmunotherapy.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) at 0 to 120, 0 to 168, and 0 to Infinity Hours | 0-120, 0-168, and 0-infinity hours from dosimetric dose (given only once on Day 0) | Area under the concentration-time curve for 131I-tositumomab from time 0 to 120, 0 to 168, and time 0 to infinity hours (extrapolated), after the end of the dosimetric dose infusion. Unit: %ID.h/mL, where %ID/mL is the percentage of the injected dose per milliliter blood. AUC measures how much drug is in the system over time after infusion. |
| Maximum Concentration (Cmax) Values | 0 to 7 days from dosimetric dose (given only once on Day 0) | Cmax is the maximum observed 131I-tositumomab concentration from time zero (end of the dosimetric dose infusion) to 7 days after the end of the infusion. Unit: %ID/mL, where %ID/mL is the percentage of the injected dose per milliliter blood. Cmax is the highest drug concentration in the blood after infusion. |
| Terminal Phase Half-life (t½) | 0 to 7 days from dosimetric dose (given only once on Day 0) | The terminal phase half-life of 131 I tositumomab in hours. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half. |
| Clearance (CL) Values | 0 to 7 days from dosimetric dose given only once on Day 0 | Clearance of 131I-tositumomab after intravenous administration. The clearance of a drug measures the rate at which the drug is removed from the body after the dose. |
| Volume of Distribution at Steady State (Vss) | 0 to 7 days from dosimetric dose given only once on Day 0 | Volume of distribution at steady state of 131I-tositumomab. Volume of distribution measures how much the drug spreads through the body after the dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Absorbed Dose in the Source Organs and the Target Organs | 0 to 7 days from dosimetric dose | The radiation absorbed dose to source organs were determined with Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM) software using residence times directly determined by an independent reviewer for kidneys, liver, lungs, spleen, urinary bladder, and total body; the radiation absorbed dose for the remaining target organs was based on a mathematical model used to calculate source organ radiation dose estimates using the same OLINDA/EXM software. OLINDA/EXM is a registered proprietary computer program. |
| Number of Participants With Expected Distribution of Radioactivity in the Circulatory System Compared With Uptake by Other Organs. | 0 to 7 days from dosimetric dose (given only once on Day 0) | Expected biodistribution (images): most radioactivity (RA) in blood pool, with uptake in normal liver and spleen less than the heart. Later time points, RA in blood pool decrease and uptake in normal liver and spleen decrease. Images may show uptake by the thyroid gland, kidneys, urinary bladder, and lungs. Altered biodistribution: Blood pool not visualized or diffuse, intense uptake in the liver and/or spleen, or uptake suggestive of urinary obstruction, diffuse lung uptake greater than the blood pool |
| Percentage of Participants Evaluable for Confirmed Response With Complete Response (CR), CR Unconfirmed (CRu), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) | From Baseline up to 99 Months | Evaluation based on the Int'l Workshop to Standardize Response Criteria for non-Hodgkin's Lymphoma (NHL). CR, complete disappearance of all detectable clinical/radiographic evidence of disease, disappearance of all disease-related symptoms if present before therapy, and normalization of biochemical abnormalities definitely assignable to NHL. CRu, complete response unconfirmed, included complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. PR, \>=50% decrease in sum of perpendicular diameters (SPD) of all measurable lesions determined at baseline. SD, less than a PR but not progressive disease (\>=50% increase from nadir in SPD for all measurable disease or the appearance of any new lesion that was \>=1.4 cm x 1.4 cm by radiographic evaluation or \>=1.0 cm by palpation per physical examination). |
| Area Under the Curve (AUC) at 0 to 120 Hours | 0-120 hours from dosimetric dose (given only once on Day 0) | Area under the concentration-time curve from time 0 to 120 hours after the end of the dosimetric dose infusion. Unit: %ID.h/mL, where %ID/mL is the percentage of the injected dose per milliliter blood. AUC measures how much drug is in the system over time after infusion. |
| Progression-free Survival | Week 7 to Week 260 post treatment | Progression-free survival, or time to progression, is defined as the time from the dosimetric dose to the first documented disease progression (PD) or death. PD is defined as a \>= 50% increase from nadir in the SPPD for all measurable disease. |
| Overall Survival | Week 7 to Week 260 post treatment | Time to death is defined as the time from the dosimetric dose to the date of death. |
| Duration of Response | Week 7 to Week 260 post treatment | Duration of response is defined as the time from first documented response (CR, CRu, or PR) until disease progression. |
| Area Under the Curve (AUC) at 0 to 168 Hours | 0-168 h from dosimetric dose (given only once on Day 0) | Ratio and 90% confidence interval for AUC(0-168) after dosimetric dose of fission-derived 131I-tositumomab to historical data from tellurium-derived 131I-tositumomab. AUC measures how much drug is in the blood over time after the dose. |
| Area Under the Curve (AUC) at 0 to Infinity (Extrapolated) | 0 to infinity h from dosimetric dose (given only once on Day 0) | Ratio and 90% CI for AUC (0 to infinity) after dosimetric dose of fission-derived 131I-tositumomab to historical data from tellurium derived 131I-tositumomab. AUC measures how much drug is in the blood over time after the dose is given. |
| Maximum Concentration (Cmax) Values | 0 to 7 days from dosimetric dose (given only once on Day 0) | Maximum observed concentration from time zero (end of the dosimetric dose infusion) to 7 days after the end of the infusion. Unit: %ID/mL, where %ID/mL is the percentage of the injected dose per milliliter blood. Cmax is the highest drug concentration in the blood after the dose. |
| Mean Residence Times From Day 0 to Day 7 | 0 to 7 days from dosimetric dose (given only once on Day 0) | Whole body images from anterior and posterior gamma camera scans were collected to assess dosimetry. Assessment of organ dosimetry required gamma camera scans from at least 4 time points. Nuclear medicine reviewers conducted a visual examination of the gamma camera scans and calculated the total body residence times. Residence time is calculated from the rate of total body clearance of iodine I-131 radioactivity during the dosimetric dose. Residence time is a measure of how long the drug resides in the body. |
Participant flow
Pre-assignment details
Blood pharmacokinetics (the primary objective), biodistribution, and organ dosimetry following a dosimetric dose of tositumomab and fission-derived iodine I-131 tositumomab in this study were compared with results following a dosimetric dose of tositumomab and tellurium-derived iodine I-131 tositumomab in a historical control group (NCT00996996).
Participants by arm
| Arm | Count |
|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab Dosimetric dose (administered only once on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) for 1 hour, followed immediately by 5 millicurie (mCi) fission-derived iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV for 20 minutes. Therapeutic dose (administered only once on Day 7): 450 mg unlabeled tositumomab administered IV for 1 hour, followed immediately by Tellurium-derived iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV for 20 minutes. The dose was calculated based on the dosimetric dose results to deliver a total body radiation dose of 75 centigray (cGy). | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Tositumomab and Fission-derived Iodine I-131 Tositumomab |
|---|---|
| Age, Continuous | 58.1 Years STANDARD_DEVIATION 12.9 |
| Race/Ethnicity, Customized Caucasian | 15 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 4 / 15 |
Outcome results
Primary
Area Under the Curve (AUC) at 0 to 120, 0 to 168, and 0 to Infinity Hours
Area under the concentration-time curve for 131I-tositumomab from time 0 to 120, 0 to 168, and time 0 to infinity hours (extrapolated), after the end of the dosimetric dose infusion. Unit: %ID.h/mL, where %ID/mL is the percentage of the injected dose per milliliter blood. AUC measures how much drug is in the system over time after infusion.
Time frame: 0-120, 0-168, and 0-infinity hours from dosimetric dose (given only once on Day 0)
Population: All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to 120, 0 to 168, and 0 to Infinity Hours | AUC(0-120) | 1.04 %ID.h/mL |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to 120, 0 to 168, and 0 to Infinity Hours | AUC(0-168) | 1.18 %ID.h/mL |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to 120, 0 to 168, and 0 to Infinity Hours | AUC(0-infinity) | 1.39 %ID.h/mL |
Primary
Clearance (CL) Values
Clearance of 131I-tositumomab after intravenous administration. The clearance of a drug measures the rate at which the drug is removed from the body after the dose.
Time frame: 0 to 7 days from dosimetric dose given only once on Day 0
Population: All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Clearance (CL) Values | 71.9 milliliters per hour (ml/hr) |
Primary
Maximum Concentration (Cmax) Values
Cmax is the maximum observed 131I-tositumomab concentration from time zero (end of the dosimetric dose infusion) to 7 days after the end of the infusion. Unit: %ID/mL, where %ID/mL is the percentage of the injected dose per milliliter blood. Cmax is the highest drug concentration in the blood after infusion.
Time frame: 0 to 7 days from dosimetric dose (given only once on Day 0)
Population: All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Maximum Concentration (Cmax) Values | 0.0189 %ID/mL |
Primary
Terminal Phase Half-life (t½)
The terminal phase half-life of 131 I tositumomab in hours. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half.
Time frame: 0 to 7 days from dosimetric dose (given only once on Day 0)
Population: All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Terminal Phase Half-life (t½) | 59.5 hours |
Primary
Volume of Distribution at Steady State (Vss)
Volume of distribution at steady state of 131I-tositumomab. Volume of distribution measures how much the drug spreads through the body after the dose.
Time frame: 0 to 7 days from dosimetric dose given only once on Day 0
Population: All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Volume of Distribution at Steady State (Vss) | 6055 milliliters (ml) |
Secondary
Area Under the Curve (AUC) at 0 to 120 Hours
Area under the concentration-time curve from time 0 to 120 hours after the end of the dosimetric dose infusion. Unit: %ID.h/mL, where %ID/mL is the percentage of the injected dose per milliliter blood. AUC measures how much drug is in the system over time after infusion.
Time frame: 0-120 hours from dosimetric dose (given only once on Day 0)
Population: All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to 120 Hours | 1.04 %ID.h/mL |
| Tellurium-Derived Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to 120 Hours | 1.07 %ID.h/mL |
90% CI: [0.85, 1.12]
Secondary
Area Under the Curve (AUC) at 0 to 168 Hours
Ratio and 90% confidence interval for AUC(0-168) after dosimetric dose of fission-derived 131I-tositumomab to historical data from tellurium-derived 131I-tositumomab. AUC measures how much drug is in the blood over time after the dose.
Time frame: 0-168 h from dosimetric dose (given only once on Day 0)
Population: All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to 168 Hours | 1.18 %ID.h/mL |
| Tellurium-Derived Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to 168 Hours | 1.24 %ID.h/mL |
90% CI: [0.83, 1.11]
Secondary
Area Under the Curve (AUC) at 0 to Infinity (Extrapolated)
Ratio and 90% CI for AUC (0 to infinity) after dosimetric dose of fission-derived 131I-tositumomab to historical data from tellurium derived 131I-tositumomab. AUC measures how much drug is in the blood over time after the dose is given.
Time frame: 0 to infinity h from dosimetric dose (given only once on Day 0)
Population: All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to Infinity (Extrapolated) | 1.39 %ID.h/mL |
| Tellurium-Derived Iodine I-131 Tositumomab | Area Under the Curve (AUC) at 0 to Infinity (Extrapolated) | 1.50 %ID.h/mL |
90% CI: [0.78, 1.1]
Secondary
Duration of Response
Duration of response is defined as the time from first documented response (CR, CRu, or PR) until disease progression.
Time frame: Week 7 to Week 260 post treatment
Population: ITT-E Population. Only participants who had a response (CR, CRu, or PR) were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Duration of Response | NA months |
Secondary
Maximum Concentration (Cmax) Values
Maximum observed concentration from time zero (end of the dosimetric dose infusion) to 7 days after the end of the infusion. Unit: %ID/mL, where %ID/mL is the percentage of the injected dose per milliliter blood. Cmax is the highest drug concentration in the blood after the dose.
Time frame: 0 to 7 days from dosimetric dose (given only once on Day 0)
Population: All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Maximum Concentration (Cmax) Values | 0.0189 %ID/mL |
| Tellurium-Derived Iodine I-131 Tositumomab | Maximum Concentration (Cmax) Values | 0.0193 %ID/mL |
90% CI: [0.87, 1.11]
Secondary
Mean Absorbed Dose in the Source Organs and the Target Organs
The radiation absorbed dose to source organs were determined with Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM) software using residence times directly determined by an independent reviewer for kidneys, liver, lungs, spleen, urinary bladder, and total body; the radiation absorbed dose for the remaining target organs was based on a mathematical model used to calculate source organ radiation dose estimates using the same OLINDA/EXM software. OLINDA/EXM is a registered proprietary computer program.
Time frame: 0 to 7 days from dosimetric dose
Population: All participants who were considered evaluable for dosimetric assessment per protocol eligibility criteria and had gamma camera scans from at least 4 time points. Different numbers of participants were analyzed for different organs (represented by n=X, X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Small Intestine | 0.24 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Osteogenic Cells | 0.44 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Adrenals | 0.25 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Ovaries | 0.25 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Heart Wall | 0.24 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Red Marrow | 0.24 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Testes | 0.21 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Skin | 0.17 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Kidneys | 0.72 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Brain | 0.19 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Spleen | 0.79 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Lower Large Intestine Wall | 0.24 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Stomach | 0.24 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Total Body | 0.23 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Liver | 0.36 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Thymus | 0.22 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Breast | 0.18 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Thyroid | 0.21 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Lungs | 0.44 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Upper Large Intestine Wall | 0.24 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Pancreas | 0.26 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Urinary Bladder Wall | 0.73 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Muscle | 0.21 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Uterus | 0.26 mGy/MBq |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Gallbladder Wall | 0.26 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Uterus | 0.27 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Total Body | 0.25 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Adrenals | 0.28 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Brain | 0.2 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Breast | 0.2 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Gallbladder Wall | 0.28 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Heart Wall | 0.26 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Kidneys | 0.92 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Lower Large Intestine Wall | 0.26 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Liver | 0.45 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Lungs | 0.61 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Muscle | 0.22 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Osteogenic Cells | 0.45 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Pancreas | 0.29 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Red Marrow | 0.20 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Skin | 0.19 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Small Intestine | 0.26 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Spleen | 0.84 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Stomach | 0.26 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Testes | 0.22 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Thymus | 0.23 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Thyroid | 0.25 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Upper Large Intestine Wall | 0.26 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Urinary Bladder Wall | 0.66 mGy/MBq |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Absorbed Dose in the Source Organs and the Target Organs | Ovaries | 0.26 mGy/MBq |
Secondary
Mean Residence Times From Day 0 to Day 7
Whole body images from anterior and posterior gamma camera scans were collected to assess dosimetry. Assessment of organ dosimetry required gamma camera scans from at least 4 time points. Nuclear medicine reviewers conducted a visual examination of the gamma camera scans and calculated the total body residence times. Residence time is calculated from the rate of total body clearance of iodine I-131 radioactivity during the dosimetric dose. Residence time is a measure of how long the drug resides in the body.
Time frame: 0 to 7 days from dosimetric dose (given only once on Day 0)
Population: All participants who were considered evaluable for dosimetric assessment per protocol eligibility criteria and had gamma camera scans from at least 4 time points. Different numbers of participants were analyzed for different organs (represented by n=X, X in the category titles).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Liver, n=10, 22 | 3.7 hours |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Lungs, n=9, 22 | 3.0 hours |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Spleen, n=10, 22 | 1.3 hours |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Kidneys, n=10, 21 | 1.5 hours |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Urinary Bladder, n=10, 22 | 1.6 hours |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Remainder of Body, n=10, 22 | 76.1 hours |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Total Body, n=10, 22 | 87.9 hours |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Remainder of Body, n=10, 22 | 81.7 hours |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Urinary Bladder, n=10, 22 | 1.4 hours |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Total Body, n=10, 22 | 95.7 hours |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Kidneys, n=10, 21 | 1.9 hours |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Lungs, n=9, 22 | 4.3 hours |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Spleen, n=10, 22 | 1.8 hours |
| Tellurium-Derived Iodine I-131 Tositumomab | Mean Residence Times From Day 0 to Day 7 | Liver, n=10, 22 | 4.7 hours |
Secondary
Number of Participants With Expected Distribution of Radioactivity in the Circulatory System Compared With Uptake by Other Organs.
Expected biodistribution (images): most radioactivity (RA) in blood pool, with uptake in normal liver and spleen less than the heart. Later time points, RA in blood pool decrease and uptake in normal liver and spleen decrease. Images may show uptake by the thyroid gland, kidneys, urinary bladder, and lungs. Altered biodistribution: Blood pool not visualized or diffuse, intense uptake in the liver and/or spleen, or uptake suggestive of urinary obstruction, diffuse lung uptake greater than the blood pool
Time frame: 0 to 7 days from dosimetric dose (given only once on Day 0)
Population: All participants who were considered evaluable for dosimetric assessment per protocol eligibility criteria and had gamma camera scans from at least 4 time points.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Number of Participants With Expected Distribution of Radioactivity in the Circulatory System Compared With Uptake by Other Organs. | 10 participants |
| Tellurium-Derived Iodine I-131 Tositumomab | Number of Participants With Expected Distribution of Radioactivity in the Circulatory System Compared With Uptake by Other Organs. | 22 participants |
Secondary
Overall Survival
Time to death is defined as the time from the dosimetric dose to the date of death.
Time frame: Week 7 to Week 260 post treatment
Population: ITT-E Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Overall Survival | NA months |
Secondary
Percentage of Participants Evaluable for Confirmed Response With Complete Response (CR), CR Unconfirmed (CRu), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD)
Evaluation based on the Int'l Workshop to Standardize Response Criteria for non-Hodgkin's Lymphoma (NHL). CR, complete disappearance of all detectable clinical/radiographic evidence of disease, disappearance of all disease-related symptoms if present before therapy, and normalization of biochemical abnormalities definitely assignable to NHL. CRu, complete response unconfirmed, included complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL. PR, \>=50% decrease in sum of perpendicular diameters (SPD) of all measurable lesions determined at baseline. SD, less than a PR but not progressive disease (\>=50% increase from nadir in SPD for all measurable disease or the appearance of any new lesion that was \>=1.4 cm x 1.4 cm by radiographic evaluation or \>=1.0 cm by palpation per physical examination).
Time frame: From Baseline up to 99 Months
Population: ITT-E Population. The individual categories for confirmed CR, confirmed CRu, etc. counts those participants who had their response confirmed by the exact same response, not those who had their response confirmed by a better response (for example, Cru to CR; PR to CR; PR to CRU; etc.).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Percentage of Participants Evaluable for Confirmed Response With Complete Response (CR), CR Unconfirmed (CRu), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) | Overall response (CR, CRu, or PR) | 67 percentage of participants |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Percentage of Participants Evaluable for Confirmed Response With Complete Response (CR), CR Unconfirmed (CRu), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) | CR | 33 percentage of participants |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Percentage of Participants Evaluable for Confirmed Response With Complete Response (CR), CR Unconfirmed (CRu), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) | PD | 7 percentage of participants |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Percentage of Participants Evaluable for Confirmed Response With Complete Response (CR), CR Unconfirmed (CRu), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) | CRu | 7 percentage of participants |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Percentage of Participants Evaluable for Confirmed Response With Complete Response (CR), CR Unconfirmed (CRu), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) | PR | 27 percentage of participants |
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Percentage of Participants Evaluable for Confirmed Response With Complete Response (CR), CR Unconfirmed (CRu), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) | SD | 7 percentage of participants |
Secondary
Progression-free Survival
Progression-free survival, or time to progression, is defined as the time from the dosimetric dose to the first documented disease progression (PD) or death. PD is defined as a \>= 50% increase from nadir in the SPPD for all measurable disease.
Time frame: Week 7 to Week 260 post treatment
Population: ITT-E Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | Progression-free Survival | 59.0 months |