Phase 2 Study of Bexxar in Relapsed/Refractory DLCL

Phase 2

Completed

Interventions: Drug: Bexxar
Drug: Acetaminophen
Drug: Diphenhydramine
Drug: Potassium Iodide (KI)

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Bexxar + Total Body Irradiation (TBI)	Potassium Iodide (KI)	Bexxar will be administered with pre-medications acetaminophen, diphenhydramine, and potassium iodide (KI).
Bexxar + Total Body Irradiation (TBI)	Acetaminophen	Bexxar will be administered with pre-medications acetaminophen, diphenhydramine, and potassium iodide (KI).
Bexxar + Total Body Irradiation (TBI)	Bexxar	Bexxar will be administered with pre-medications acetaminophen, diphenhydramine, and potassium iodide (KI).
Bexxar + Total Body Irradiation (TBI)	Diphenhydramine	Bexxar will be administered with pre-medications acetaminophen, diphenhydramine, and potassium iodide (KI).

Primary Outcome Measures

Name	Time	Method
Clinical Response Rate	6 years	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.

Secondary Outcome Measures

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