Safety and Efficacy Study of I-131 Tositumomab in Patients With Relapsed/Refractory Hodgkin's Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to find the highest safe dose of Iodine-131 Tositumomab (Bexxar®) that can be given to patients who have relapsed/refractory Hodgkin's lymphoma, what side effects these patients get when they take Bexxar® and if Bexxar® is effective in treating relapsed/refractory Hodgkin's lymphoma. Bexxar® works by delivering doses of radiation to cancer cells.

Detailed Description
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One third of patients with Hodgkin's lymphoma (HL) do not respond to or have their disease come back after their first therapy. These patients often then receive high-dose chemotherapy and blood or marrow transplant. Despite high response rates after transplant, a significant number, 26-65%, of these patients have their disease come back again. After transplant, therapy options are limited and alternative therapies for patients with HL who have relapsed post-transplant or who are ineligible for transplant are needed. Based on recent studies about how HL develops and good results of patient studies evaluating the use of the unlabeled anti-CD20 antibody Rituximab in HL, we think that radioimmunotherapy (RIT) with I-131 Tositumomab(Bexxar®) will be an effective alternative therapy in patients with relapsed/refractory HL who are post or ineligible for transplant. The rationale for the use of RIT in cancer is that radiolabeled monoclonal antibodies will specifically target and irradiate tumor cells but not normal tissues. The specific tumor targeting of RIT theoretically allows higher doses of radiation to be delivered to tumor as compared to external beam radiation because the effects of the radiation on normal tissues is less with RIT. Iodine-131 Tositumomab (Bexxar®) was approved by the FDA for another type of lymphoma in 2003. The antibody (Tositumomab) recognizes and attaches to a protein on lymphoma cells and can kill these cells. The radioisotope (I-131) can help the antibody kill cells better. Iodine-131 Tositumomab (Bexxar®) is given through a vein in the arm. Iodine-131 Tositumomab (Bexxar®) is given in an outpatient setting.

Official Title
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A Phase I/II Study of I-131 Tositumomab in Patients With Relapsed/Refractory Hodgkin's Lymphoma

Conditions
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Hodgkin's Disease

Intervention / Treatment
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* Drug: I-131 Tositumomab therapeutic regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven Hodgkin's lymphoma that is relapsed or refractory and the patient has previously had a transplant or is ineligible for transplant All stages and histologic subtypes of Hodgkin's lymphoma Malignant cells may be CD20+ or CD20- May have previously had either a non-myeloablative or myeloablative allogeneic or autologous stem cell transplant If prior history of greater than 1 transplant, eligible if other entry criteria are met No upper limit on the amount of prior chemotherapy Must be at least 4 weeks out from their most recent chemotherapy or radiation therapy, 6 weeks if the last regimen included BCNU, or mitomycin Age 18 or greater Karnofsky performance status ≥ 60 Organ and marrow function within 4 weeks of registration on the protocol as defined below: Leukocytes >2,000/mm3 Absolute neutrophil count >1,000/ mm3 Platelets >75,000/ mm3 Hemoglobin >7 g/dL Creatinine <2.5 mg/dL Less than 25% bone marrow involvement with Hodgkin's lymphoma within 4 weeks of registration on the protocol If female, not pregnant or breast feeding Ability to understand and the willingness to sign a written informed consent document At least one measurable target lesion, measuring 1.5 cm in at least one dimension by standard CT imaging which is FDG -avid on PET/CT. 2-year expected survival from other diseases Exclusion Criteria: Receiving any other investigational agents at the same time Hypocellular bone marrow (less than or equal to 10% cellularity) or marked decrease in any one (or more) hematopoietic precursor within 4 weeks of registration on the protocol Inability to follow basic radiation safety precautions Active infections requiring intravenous antibiotics until after resolution of the infection

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A Single Dose of I-131 Tositumomab<br>I-131 Tositumomab therapeutic regimen given to patients with relapsed/refractory Hodgkin's lymphoma who have or have not undergone transplant. | Drug: I-131 Tositumomab therapeutic regimen<br>* Tositumomab and I-131 tositumomab are given intravenously. A test dose is given followed by a larger treatment dose.<br>* Other names: Brand name: Bexxar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-myeloablative Maximum Tolerated Dose of I-131 Tositumomab That Can be Given to Patients With Relapsed/Refractory Hodgkin's Lymphoma. |  | 2 years | 
| Overall and Complete Response Rates | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CTI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 12 weeks post therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Progression Following I-131 Tositumomab Therapy. |  | From time measurement criteria are met for response until first date that recurrent or progressive disease is objectively documented, assessed up to 5 years. | 
| Frequency of Visualization of Hodgkin's Lymphoma With I-131 Tositumomab Imaging and Tumor Radiation Absorbed Dose | Percentage of participants with visualized I-131 uptake. | up to 1 week post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin's lymphoma, Radioimmunotherapy, Bexxar, I-131 Tositumomab, Safety, Efficacy, Nuclear Medicine, Monoclonal antibody, Radiolabeled