Study of Bexxar <Tositumomab> Combined With External Beam Radiation Therapy

Study Overview
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Brief Summary
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The purpose of the study is to assess the response rate of patients with relapsed or refractory low-grade or transformed low-grade, CD20-positive, B-cell non-Hodgkin's lymphoma to Iodine-131 (I-131) tositumomab (Bexxar) therapy plus local palliative radiation therapy (XRT).

Detailed Description
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Response will be assessed on the basis of the presence or absence of measurable lesion ≥ 1.4 x 1.4 cm (operationally defined as ≥ 2.0 cm2) by radiographic evaluation OR ≥ 1.0 cm in greatest diameter detected by palpation on physical exam

Official Title
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Study of Bexxar <Tositumomab> Combined With External Beam Radiation Therapy for Patients With Relapsed, Bulky Non-Hodgkin's Lymphoma

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: Bexxar (tositumomab)
* Procedure: External beam radiotherapy (XRT)
* Drug: Potassium Iodide (KI)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Histologically confirmed low grade CD20+ B cell non-Hodgkin lymphoma (NHL) patients who have relapsed after chemotherapy or are chemotherapy resistant and have one or more sites of disease measuring more than 5 cm. The patients must have failed at least one chemotherapy regimen No anticancer treatment for three weeks prior to study initiation (six weeks if Rituximab, nitrosourea or Mitomycin C) Fully recovered from all toxicities associated with prior surgery, radiation, chemotherapy or immunotherapy An institutional review board- (IRB)-approved signed informed consent Age 19 years or older Expected survival of at least 6 months Prestudy Performance Status of 0, 1 or 2 according to the World Health Organization (WHO) Absolute neutrophil count (ANC) of at least 1,500/mm³ Platelet count at least 100,000/mm³ Hct > 30% Hgb > 9.0 gm Bilirubin ≤ 2.0 Creatinine ≤ 2.0 Bone marrow involvement with lymphoma less than 25% (bilateral bone marrow) within 6 weeks of enrollment Acceptable birth control method for men and women EXCLUSION CRITERIA Disease progression within 3 months of last chemotherapy Prior myeloablative therapies with bone marrow transplantation or peripheral stem cell rescue Platelet count less than 100,000/mm³ Hypocellular bone marrow (≤ 15% cellularity) Marked reduction in bone marrow precursors of one or more cell lines History of failed stem cell collection Prior treatment with fludarabine Prior radioimmunotherapy Presence of central nervous system (CNS) lymphoma HIV or AIDS-related lymphoma Evidence of myelodysplasia on bone marrow biopsy Abnormal bone marrow cytogenetics Patients who have received prior external beam radiation therapy to more than 25% of active bone marrow Patients who have received filgrastim Sargramostim therapy within 3 weeks prior to treatment Presence of human anti-mouse antibody (HAMA) reactivity in patients with prior exposure to murine antibodies or proteins Serious nonmalignant disease or infection, which, in the opinion of the investigator and/or sponsor, would compromise other protocol objectives Another primary malignancy (other than squamous cell and basal cell cancer of the skin, in situ carcinoma of the cervix, or treated prostate cancer with stable prostate-specific antigen, PSA) for which the patients has not been disease free for at least 3 years Major surgery, other than diagnostic surgery within 4 weeks Pleural effusion Pregnant Lactating

Ages Eligible for Study
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Minimum Age: 19 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tositumomab + XRT + KI<br>Tositumomab + external beam radiotherapy (XRT) + potassium iodide (KI) | Drug: Bexxar (tositumomab)<br>* Tositumomab is a CD20-directed radiotherapeutic (131-iodine) monoclonal antibody indicated for the treatment of patients with CD20-positive, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin's lymphoma who have progressed during or after rituximab therapy, including patients with rituximab-refractory non-Hodgkin's lymphoma. Tositumomab (standard regimen) will be administered at whole body exposure of 75 cGy.<br>* Other names: 131-iodine tositumomab;Procedure: External beam radiotherapy (XRT)<br>* Patient-specific XRT will begin within 24 hours of administration of the therapeutic dose of tositumomab. Subjects will receive local XRT to bulky sites of disease measuring at least 5 cm in at least one dimension. The size and number of fields to be treated will determined by the investigators, but will encompass the patient's most symptomatic/threatening site(s) of disease and not cumulatively include more than 25% of the active bone marrow. Subjects will be treated with the 2 x 2 Gy regimen (2 daily fractions of 2 Gy). Sites of disease previously-irradiated with 30 to 40 Gy will not be treated on this study.<br>* Other names: Radiotherapy (RT);Drug: Potassium Iodide (KI)<br>* Potassium iodide (KI) will be administered as: Saturated solution potassium iodide (SSKI) 4 drops orally 3-times-a-day, Lugol's solution 20 drops orally 3-times-a-day, OR KI tablets 130 mg orally once per day KI treatment will start at least 24 hours prior to tositumomab, and continue daily for 14 days following the last dose of tositumomab<br>* Other names: Potassium iodide tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) Rate | Participants assessed for by the following Complete Response (CR) criteria CR or Functional CR No evidence of disease and symptoms Any macroscopic nodules detected in any organs no longer present. Any palpable lymph node is normal and greatest diameter is < 1.0 cm. The enlarged organs decreased in size and not palpable The bone marrow biopsy and aspirate are negative for disease Negative for disease by PET-scan (functional CR) CR Unconfirmed (CRu) criteria No evidence of disease and symptoms Any lymph node mass > 1.0 cm^2 diameter has regressed is size by more than 75%. No macroscopic nodules in any organs Any palpable lymph node is normal and greatest diameter is < 1.0 cm. The bone marrow biopsy and aspirate are negative for disease The bone marrow biopsy may have increased number or size of lymphoid aggregates without cytologic or architectural atypia | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR is assessed as the sum of the overall rates of CR confirmed by positron emission tomography (PET) CR not confirmed by PET, and Partial response (PR) negative for progression by PET | 12 weeks | 
| Time-to-Progression (TTP) |  | 2 years |