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

NCT00315731 | Completed Phase 1 Results

• 1 other identifier: 393229/027
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Lymphoma, Follicular

Keywords

Bexxar; tositumomab and iodine I 131 tositumomab therapeutic regiment; fission; Non-Hodgkin's lymphoma; Iodine I 131 Tositumomab; pharmacokinetics; tellurium

Outcome Measures

Primary Outcomes (5)

• 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.

  0-120, 0-168, and 0-infinity hours from dosimetric dose (given only once on Day 0)

• 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.

  0 to 7 days from dosimetric dose (given only once on Day 0)

• 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.

  0 to 7 days from dosimetric dose (given only once on Day 0)

• 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.

  0 to 7 days from dosimetric dose given only once on Day 0

• 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.

  0 to 7 days from dosimetric dose given only once on Day 0

Secondary Outcomes (11)

• 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 Curve (AUC) at 0 to 168 Hours

  0-168 h from dosimetric dose (given only once on Day 0)

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

  0 to infinity h from dosimetric dose (given only once on Day 0)

• Maximum Concentration (Cmax) Values

  0 to 7 days from dosimetric dose (given only once on Day 0)

• Mean Residence Times From Day 0 to Day 7

  0 to 7 days from dosimetric dose (given only once on Day 0)

Study Arms (1)

tositumomab and iodine I 131 tositumomab

EXPERIMENTAL

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.

Biological: Follicular Lymphoma

Interventions

Follicular Lymphoma BIOLOGICAL

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

tositumomab and iodine I 131 tositumomab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• 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.
• Stage III or IV disease at the time of study entry (based on Ann Arbor Staging Classification)
• 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
• Performance status of at least 70% on the Karnofsky Performance Scale and an anticipated survival of at least 3 months.
• 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
• 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
• 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
• 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
• HAMA negative within 21 days prior to study enrollment
• Signed IRB approved consent form prior to any study-specific procedures being implemented

You may not qualify if:

• 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
• 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.)
• Prior rituximab therapy within 120 days prior to study enrollment
• Prior radioimmunotherapy
• Prior splenectomy
• 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
• Bulky disease as defined as any uni-dimensional measurement of lymphomatous mass exceeding 7 cm
• 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%
• Central nervous system involvement by lymphoma
• Evidence of active infection requiring IV antibiotics at the time of study enrollment
• Known human immunodeficiency virus (HIV) infection
• New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation.
• Active obstructive hydronephrosis
• Evidence of clinically significant ascites or pleural effusion observed on screening physical examination or baseline CT scan

Sponsors & Collaborators

• GlaxoSmithKline: lead

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study 393229/027 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2006
• First Posted: April 19, 2006
• Study Start: March 31, 2003
• Primary Completion: December 4, 2006
• Study Completion: June 30, 2013
• Last Updated: July 11, 2017
• Results First Posted: April 23, 2012

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share