A Study Of Pharmacokinetics, Whole Body And Organ Dosimetry, And Biodistribution Of Fission-Derived Iodine I 131 Tositumomab (BEXXAR®) For Patients With Previously Untreated Or Relapsed Follicular Or Transformed Non-Hodgkin's Lymphoma
- Conditions
- Lymphoma, Follicular
- Interventions
- Biological: Follicular Lymphoma
- Registration Number
- NCT00315731
- Lead Sponsor
- GlaxoSmithKline
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description tositumomab and iodine I 131 tositumomab Follicular Lymphoma Subjects participating in this study will receive a standard 5 mCi dosimetric dose of fission-derived Iodine I-131 tositumomab, immediately following an infusion of 450 mg of unlabeled tositumomab. Using the dosimetric data from three of the six imaging time points and the subject's weight, a patient-specific activity (mCi) of Iodine I-131 will be calculated to deliver the desired total body dose of radiation (75 cGy). All subjects will then receive an infusion of unlabeled tositumomab (450 mg) immediately followed by an infusion of the subject specific dose of tellurium-derived Iodine I-131 tositumomab (35 mg) to deliver a total body dose (TBD) of 75 cGy.
- Primary Outcome Measures
Name Time Method 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.
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.
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.
- Secondary Outcome Measures
Name Time Method 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.
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.
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.
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.
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.
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).
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 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.
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
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.