Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Follicular Lymphoma

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Iodine

Cadexomer iodine

Tositumomab I-131

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.

For subjects with previously untreated or relapsed follicular or transformed follicular non-Hodgkin's

GSK Clinical Trials

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.

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

A Multi-Center Study to Examine the Pharmacokinetics, Whole Body and Organ Dosimetry, and Biodistribution of Fission-Derived Iodine I 131 Tositumomab for Patients With Previously Untreated or Relapsed Follicular or Transformed Follicular Non-Hodgkin's Lymphoma

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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.

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.

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 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 of 131I-tositumomab. Volume of distribution measures how much the drug spreads through the body after the dose.

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.

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.

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 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.

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.

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.

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

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 is defined as the time from first documented response (CR, CRu, or PR) until disease progression.

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 to death is defined as the time from the dosimetric dose to the date of death.

GlaxoSmithKline

An on-therapy adverse event (AE) is an AE that occurred from the time of enrollment until 26 weeks after the dosimetric dose (DD) or until administration of subsequent therapy for lymphoma, whichever occurred first. After Week 26, AEs were reported if considered by the investigator to be possibly associated with the iodine I-131 tositumomab DD.

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).

Tositumomab and Fission-derived Iodine I-131 Tositumomab

Age, Continuous

Sex: Female, Male

Caucasian

Race/Ethnicity, Customized

GSK Response Center

AUC(0-120)

AUC(0-168)

AUC(0-infinity)

All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.

Area Under the Curve (AUC) at 0 to 120, 0 to 168, and 0 to Infinity Hours

Maximum Concentration (Cmax) Values

Terminal Phase Half-life (t½)

Clearance (CL) Values

Volume of Distribution at Steady State (Vss)

Evaluable participant data from the historical trial, Study RIT II 003 (NCT01224821), in which participants received tisitumomab and tellurium-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) tellurium-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).

Tellurium-Derived Iodine I-131 Tositumomab

Area Under the Curve (AUC) at 0 to 120 Hours

Evaluable participant data from the historical trial, Study RIT II 003 (NCT01224821), in which participants received tisitumomab and tellurium-derived iodine I-131 tositumomab Dosimetric dose (administered on Day 0): 450 milligrams (mg) unlabeled tositumomab administered intravenously (IV) for 1 hour, followed immediately by 5 millicurie (mCi) tellurium-derived iodine I-131 tositumomab (contained in 35 mg tositumomab) administered IV for 20 minutes. Therapeutic dose (administered 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).

Area Under the Curve (AUC) at 0 to 168 Hours

Area Under the Curve (AUC) at 0 to Infinity (Extrapolated)

Total Body, n=10, 22

Kidneys, n=10, 21

Liver, n=10, 22

Lungs, n=9, 22

Spleen, n=10, 22

Urinary Bladder, n=10, 22

Remainder of Body, n=10, 22

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).

Mean Residence Times From Day 0 to Day 7

Total Body

Adrenals

Brain

Breast

Gallbladder Wall

Heart Wall

Kidneys

Lower Large Intestine Wall

Liver

Lungs

Muscle

Osteogenic Cells

Ovaries

Pancreas

Red Marrow

Skin

Small Intestine

Spleen

Stomach

Testes

Thymus

Thyroid

Upper Large Intestine Wall

Urinary Bladder Wall

Uterus

Mean Absorbed Dose in the Source Organs and the Target Organs

All participants who were considered evaluable for dosimetric assessment per protocol eligibility criteria and had gamma camera scans from at least 4 time points.

Number of Participants With Expected Distribution of Radioactivity in the Circulatory System Compared With Uptake by Other Organs.

Overall response (CR, CRu, or PR)

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.).

Percentage of Participants Evaluable for Confirmed Response With Complete Response (CR), CR Unconfirmed (CRu), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD)

ITT-E Population. Only participants who had a response (CR, CRu, or PR) were evaluated.

Spots Global Cancer Trial Database for tositumomab and iodine i 131 tositumomab therapeutic regiment