A Comparative Study Of Iodine I 131 Tositumomab Therapeutic Regimen Versus Ibritumomab Tiuxetan Therapeutic Regimen

Study Overview
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Brief Summary
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This is a multi-center, randomized, study to compare Iodine I 131 Tositumomab therapeutic regimen to Ibritumomab Tiuxetan therapeutic regimen in the treatment of patients with relapsed or transformed follicular non-Hodgkin's B-cell lymphoma. A total of 350 patients, approximately 175 patients per arm, will be enrolled at 30 to 40 sites in the United States.

Official Title
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A Multi-center, Randomized, Phase 3 Study of Iodine I 131 Tositumomab Therapeutic Regimen Versus Ibritumomab Tiuxetan Therapeutic Regimen for Patients With Relapsed or Transformed Follicular Non-Hodgkin's Lymphoma

Conditions
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Lymphoma, Small Cleaved-Cell, Follicular, Lymphoma, Large-Cell, Follicular, Lymphoma, Follicular, Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: Ibritumomab Tiuxetan
* Drug: Iodine I 131 Tositumomab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 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 of 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. Patients diagnosed with diffuse large cell lymphoma at study enrollment must have a historical or contemporaneous lymph node biopsy that demonstrates a diagnosis of follicular lymphoma. Recurrent lymphoma after at least three qualifying therapy regimens including at least one Rituximab-containing regimen and at least one chemotherapy regimen. The patient must have either not responded or responded with a duration of response of less than 6 months to a Rituximab-containing regimen, Performance status of at least 70% on the Karnofsky Scale and an anticipated survival of at least three months. Bi-dimensionally measurable disease with at least one lesion measuring 4.0 cm2 by CT scan. Absolute neutrophil count >/= 1500 cells/mm3 and platelet count >/=100,000/mm3 within 21 days prior to study enrollment. Blood products and/or growth factors should not be taken within 4 weeks prior to blood draw. Adequate renal function (defined as serum creatinine <1.5 x upper limit of normal) and adequate hepatic function (defined as total bilirubin <1.5x upper limit of normal and AST <5x upper limit of normal) within 21 days prior to study enrollment. Human Anti-Murine Antibody (HAMA) negative within 21 days prior to study enrollment. Provision of informed consent as signified by a signed IRB approved consent form prior to any study-specific procedures being implemented. Exclusion criteria: Greater than 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically within 90 days prior to study enrollment. Hypocellular bone marrow (</=15% cellularity or marked reduction in bone marrow precursors). Prior myeloablative therapy. History of failed stem cell collection. Prior radiotherapy to fields encompassing more than 25% of the blood forming marrow. Prior chemotherapy, biologic therapy, radiation therapy or steroid therapy for NHL within eight weeks prior to screening procedures. Prior radioimmunotherapy. Prior treatment with any non-human, particularly murine monoclonal or polyclonal antibodies for either diagnostic or therapeutic purposes. This exclusion does not extend to the chimeric monoclonal antibody, Rituximab. Prior malignancy other than lymphoma, except for adequately treated basal cell or squamous cell skin cancer, in situ uterine cervical cancer, or other cancer for which the patient has been disease-free for five years. Active infection requiring intravenous antibiotics at the time of study enrollment. New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation. HBsAg seropositivity. Known HIV infection. Known brain or leptomeningeal metastases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ibritumomab Tiuxetan|nan|
|Drug: Iodine I 131 Tositumomab|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the proportion of subjects experiencing Grade 3/4 hematological toxicity within 120 days from completion of treatment regimen administration. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The final analysis will be carried out when 130 events (progressive disease, death or subsequent therapy) have occurred in the control arm, expected approximately 18 months after last subject last visit. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-Hodgkin's Lymphoma, follicular lymphoma, BEXXAR, ZEVALIN, Iodine I 131 Tositumomab, Ibritumomab Tiuxetan, Follicular, mixed small-cleaved and large-cell, Diffuse large cell non-Hodgkin's lymphoma following or concurrent with a diagnosis of follicular lymphoma