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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 currently recruiting participants.
Verified by GlaxoSmithKline, June 2008
Sponsored by: 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
Non-Hodgkin's Lymphoma
Follicular Lymphoma
Diffuse Large Cell Lymphoma
Drug: Iodine I 131 Tositumomab Therapeutic Regimen
Phase I
Phase II

MedlinePlus related topics: Cancer Lymphoma
Drug Information available for: Iodine Cadexomer iodine Sodium iodide I 131 Tositumomab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Historical Control, Single Group Assignment, Bio-equivalence Study
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

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: up to 10 years ]
  • Comparison of the fission-derived Iodine I-131 tositumomab blood pharmacokinetics, total body clearance, and tumor and organ dosimetry, and biodistribution with tellurium-derived blood pharmacokinetics
  • Total body clearance, and tumor and organ dosimetry using available historical control data
  • Safety will be analyzed for all subjects receiving study drug. Adverse experiences will be summarized by body system, severity and relationship to study drug
  • Subject discontinuations and clinical laboratory abnormalities will be summarized. The use of supportive care measures such as CSF and transfusions will also be presented. Long-term safety and survival will be summarized.

Estimated Enrollment: 12
Study Start Date: May 2003
Estimated Study Completion Date: February 2016
  Eligibility

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

Inclusion criteria:

  • At least 18 years of age.
  • A histologically confirmed diagnosis of: Follicular lymphoma, Grade 1, 2, or 3, or diffuse large cell lymphoma concurrent with or following the diagnosis of follicular lymphoma (WHO/REAL classification).International Working Formulation histological equivalents include:

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.
  • Previously untreated or recurrent lymphoma after no more than four prior qualifying therapy regimens. Qualifying chemotherapy can be found in Section 13.1, Appendix A. Steroids alone, as treatment for lymphoma, do not constitute a treatment regimen
  • Performance status of at least 70% on the Karnofsky Performance Scale and an anticipated survival of at least three months. The Karnofsky Performance Scale can be found in Section 13.2, Appendix B.
  • Bi-dimensionally measurable disease with at least one lesion measuring ≥2.0 cm x 2.0 cm (≥4.0 cm2) by CT scan
  • Absolute B lymphocyte count (as determined by CD19 reactivity) of 30 to 350 cell/mm3 within 21 days prior to study enrollment
  • Absolute neutrophil count ≥1500 cells/mm3; platelet count ≥150,000/mm3; and hemoglobin ≥10 g/dL within 21 days prior to study enrollment. Blood products and/or growth factors should not have been 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
  • Human anti-murine antibody (HAMA) negative within 21 days prior to study enrollment
  • Signed IRB approved consent form prior to any study-specific procedures being implemented
  • Follicular lymphoma (i.e., Grade 1,2, or 3), or diffuse large cell lymphoma concurrent with or following the diagnosis of follicular lymphoma, including follicular small cleaved, follicular mixed small-cleaved & large cell; follicular large-cell; or transformed diffuse large cell lymphoma following or concurrent with a diagnosis of follicular lymphoma.
  • KPS>/=70%.
  • Bidimensionally measureable disease with at least one lesion >/= 2.0 cm x 2.0 cm by CT scan.
  • platelet count>/=150,000/mm3; and hemoglobin =10 g/dl within 21 days prior to study enrollment. Note: Blood products and/or growth factors should not have been taken within 4 weeks prior to blood draw.

Exclusion criteria:

  • 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 is adequate. The marrow core should be ≥2.0 cm in length. The procedure for bone marrow biopsy analysis of marrow involvement is found in Section 13.3, Appendix C.
  • 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 may enter this study. ("Low dose steroids" is defined as ≤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 is defined as: Spleen mass = π (X x Y x Z) / 6 Where X and Y are the greatest perpendicular diameters in cm on any single computerized axial tomography (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 unidimensional 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 has 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. Criteria can be found in Section 13.4, Appendix D.
  • Active obstructive hydronephrosis.
  • Evidence of clinically significant ascites or pleural effusion observed on screening physical exam or baseline CT scan.
  • Prior myeloablative therapy.
  • History of failed stem cell collection.
  • Pregnant or nursing patients. Subjects of childbearing potential must have a negative serum pregnancy test within 21 days of study enrollment. Males and females of childbearing age must agree to use effective contraception for up to 12 months following the radioimmunotherapy.
  • 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.
  • Prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for their NHL within 28 days prior to study enrollment.
  • Bulky disease as defined as any unidimensional 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 patient has a generally accepted risk of recurrence less than 20%.
  • CNS involvement by lymphoma.
  • Active infection requiring IV antibiotics at study enrollment.
  • Active obstructive hydronephrosis.
  • Evidence of clinically significant ascites or pleural effusion observed on screening physical exam or baseline CAT scan.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00315731

Locations
United States, Florida
GSK Clincial Trials Call Center Active, not recruiting
Bay Pines, Florida, United States, 33708
United States, Illinois
GSK Clinical Trials Call Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Stephanie Gregory     877-379-3718        
United States, Michigan
GSK Clinical Trials Call Center Active, not recruiting
Ann Arbor, Michigan, United States, 48109
United States, Nebraska
GSK Clinical Trials Call Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Julie Vose     877-379-3718        
United States, North Carolina
GSK Clinical Trials Call Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Joe Gockerman     877-379-3718        
United States, Pennsylvania
GSK Clinical Trials Call Center Active, not recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MD GlaxoSmithKline
  More Information

Study ID Numbers: 393229/027, CCBX001-048
Study First Received: April 17, 2006
Last Updated: June 9, 2008
ClinicalTrials.gov Identifier: NCT00315731  
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Non-Hodgkin's lymphoma
pharmacokinetics
bioequivalence
Iodine I 131 Tositumomab
tellurium
fission
Bexxar
Iodine I 131 Tositumomab Therapeutic Regimen

Study placed in the following topic categories:
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Iodine-131 anti-B1 antibody
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Antibodies, Monoclonal
Lymphoma, B-Cell
Lymphoma, large-cell
Lymphatic Diseases
Antibodies
B-cell lymphomas
Iodine
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma
Follicular lymphoma
Immunoglobulins

Additional relevant MeSH terms:
Anti-Infective Agents
Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Trace Elements
Pharmacologic Actions
Anti-Infective Agents, Local
Neoplasms
Therapeutic Uses
Micronutrients

ClinicalTrials.gov processed this record on January 16, 2009