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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
This study is ongoing, but not recruiting participants.

First Received on April 17, 2006.   Last Updated on October 21, 2010   History of Changes
Sponsor: GlaxoSmithKline
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00315731
  Purpose

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.


Condition Intervention Phase
Follicular Lymphoma
Lymphoma, Follicular
Non-Hodgkin's Lymphoma
Biological: Follicular Lymphoma
Phase II

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To assess blood pharmacokinetics in patients with previously untreated or relapsed follicular or transformed follicular non-Hodgkin's lymphoma who have received a dosimetric dose of fission-derived Iodine I 131 Tositumomab. [ Time Frame: 2 Weeks ]

Secondary Outcome Measures:
  • Assess fission-derived Iodine I 131 Tositumomab total body clearance, tumor, and organ dosimetry, and biodistribution.Compare these with same from patients treated with tellurium-derived Iodine I 131 Tositumomab using historical control data. [ Time Frame: 2 Weeks ]
  • Safety and Efficacy will be analyzed for all subjects receiving study drug. Adverse experiences will be summarized by body system, severity andrelationship to study drug [ Time Frame: 10 years ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: March 2003
Estimated Study Completion Date: November 2016
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tositumomab and iodine I 131 tositumomab
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
For subjects with previously untreated or relapsed follicular or transformed follicular non-Hodgkin's

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00315731

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00315731     History of Changes
Other Study ID Numbers: 393229/027, CCBX001-048
Study First Received: April 17, 2006
Last Updated: October 21, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Bexxar
tositumomab and iodine I 131 tositumomab therapeutic regiment
fission
Non-Hodgkin's lymphoma
Iodine I 131 Tositumomab
pharmacokinetics
tellurium

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Iodine
Cadexomer iodine
Iodine-131 anti-B1 antibody
Antibodies, Monoclonal
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents
Immunologic Factors

ClinicalTrials.gov processed this record on February 09, 2012