Phase 2 Study of Bexxar in Relapsed/Refractory DLCL

Study Overview
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Brief Summary
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The purpose of this study is to obtain safety and efficacy data using Bexxar in patients with relapsed/refractory diffuse large cell Non-Hodgkin's lymphoma (DLCL).

Detailed Description
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There is a lack of efficacious treatment options for patients with relapsed/refractory diffuse large cell Non-Hodgkin's lymphoma (DLCL) who are not appropriate candidates for stem cell transplantation. DLCL is a relatively radiosensitive disease and patients with DLCL have been reported to respond to anti-CD20 monoclonal antibody (MAB) therapy. Therefore, radioimmunotherapy targeting CD20 is a rational and promising therapeutic approach for this patient population. This study evaluated if Bexxar is safe and efficacious for diffuse large cell Non-Hodgkin's lymphoma.

Official Title
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Phase 2 Study of Bexxar in Relapsed/Refractory Diffuse Large Cell Lymphoma (DLCL)

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: Bexxar
* Drug: Acetaminophen
* Drug: Diphenhydramine
* Drug: Potassium Iodide (KI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed, diffuse large cell lymphoma (DLCL), CD20+ B-cell non-Hodgkin lymphoma (NHL) who have relapsed after chemotherapy or are chemotherapy resistant, without prior history of low grade NHL. The patient must have failed at least one chemotherapy regimen containing an anthracycline or equivalent chemotherapeutic agent. No anticancer treatment for three weeks prior to the treatment dose of Bexxar (6 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 Prestudy Karnofsky Performance Status of ≥ 70% Absolute neutrophil count (ANC) ≥ 1,500/mm³ Platelet count ≥ 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 Female patients who are not pregnant Not lactating Exclusion Criteria: Prior myeloablative therapies with bone marrow transplantation or peripheral stem cell rescue Platelet count < 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 Patients with known HIV or AIDS-related lymphoma Patients with evidence of myelodysplasia on bone marrow biopsy Patients who have received prior external beam radiation therapy to more than 25% of active bone marrow Patients who have received filgrastim or sargramostim therapy within 3 weeks prior to treatment Pregnant Lactating 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, would compromise other protocol objectives Another primary malignancy (other than squamous cell and basal cell carcinoma of the skin, in situ carcinoma of the cervix, or treated prostate cancer with stable prostate specific antigen levels) for which the patients has not been disease-free for at least 3 years Major surgery, other than diagnostic surgery, within 4 weeks Patients with pleural effusion

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: Bexxar + Total Body Irradiation (TBI)<br>Bexxar will be administered with pre-medications acetaminophen, diphenhydramine, and potassium iodide (KI). | Drug: Bexxar<br>* Bexxar is a radioimmunotherapeutic drug, an antibody that specifically attaches to the CD20 antigen, which is present on the surfaces of B cells and B cell lymphoma cells. The radioactive isotope then gives off radiation, which kills the cells. Bexxar will be administered to provide the following patient-specific radiotherapy: Platelet count of 150,000/mm³ = 75 cGy Platelet count ≥ 100,000/mm³ but < 150,000/mm³ = 65 cGy<br>* Other names: I-131 tositumomab;Drug: Acetaminophen<br>* As premedication 30 to 60 minutes before antibody infusion; 650 mg, oral. Used to as to relieve pain<br>* Other names: Tylenol;Drug: Diphenhydramine<br>* As premedication 30 to 60 minutes before antibody infusion; 50 mg, oral. Used to prevent inflammation or allergic reactions<br>* Other names: Benadryl;Drug: Potassium Iodide (KI)<br>* Administered to prevent thyroid blockage 130 mg orally 3 times a day,<br>* Other names: Lugol's solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response Rate | Clinical response rate for all participants, reported as the sum of the numbers of patients achieving complete response (CR, complete disappearance of all lesions); functional CR (fCR, minimal residual disease but clear of disease by positron emission tomography (PET)-scan); or partial response (PR, ≥ decrease in size of lesions and negative for active disease by PET-scan). Progressive disease (PD, advancing cancer) or stable disease (not CR, fCR, or PD) not included as Clinical Response. | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TTP) | Time of disease progression reported as the number of subjects experiencing disease progression at the time point of progression. | 1.5 months; 3 months; 6 months; or Not Progressed | 
| Overall Survival (OS) Rate | Overall survival reported as the percentage of participants (less lost-to-follow-up) surviving at 6 years. | 6 years |