Safety and Efficacy of Bexxar Therapy in the Treatment of Relapsed/Residual B-Cell Lymphoma After Autologous Transplant

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become
the standard of care for relapsed/refractory chemotherapy-sensitive non-Hodgkin's lymphomas
(NHL). However, one-half to two-thirds of such patients will relapse after ASCT, with
subsequent poor prognosis, and new therapies are urgently needed for this patient
population. Radioimmunotherapy (RIT) as a single agent therapy in patients with CD20
antigen-expressing relapsed or refractory low-grade, follicular, or transformed NHL has
demonstrated overall response rates of 60-80% and has been approved by the FDA for use in
this setting. While RIT is currently under investigation as a component of conditioning
regimens for ASCT, the safety and efficacy of RIT after ASCT has not yet been well
described. We will conduct a single-center Phase I dose-escalation trial of Bexxar
(Tositumomab and 131I Tositumomab) for treatment of relapsed or residual CD20
antigen-expressing B-cell lymphomas following ASCT. Our primary aim will be to determine the
safety, dose-limiting toxicity, and maximum tolerated dose of Bexxar in this post-ASCT
patient population. Our secondary aim will be to describe the overall response rate,
progression-free survival, time to treatment failure, and overall survival. Should Bexxar
prove to be safe in this population, subsequent trials will be designed to investigate
further the efficacy of RIT in the post-transplant setting.

Inclusion Criteria:

- CD20 positive B-cell lymphoma

- Confirmed relapsed/refractory disease following autologous transplant

- Age ≤ 75 years

- Performance status 0 or 1

- Creatinine ≤ 1.5 or calculated creatinine clearance ≥ 60 ml/min

- Total bilirubin, AST, and ALT ≤ 1.5 x upper limit of normal (unless bilirubin due to
Gilbert's)

- No active CNS disease

- No detectable bone marrow involvement by lymphoma on histopathologic bone marrow
examination

- Bone marrow cellularity ≥ 15% on histopathologic bone marrow examination

- Availability of adequate stored autologous stem cell product (≥ 2 x 106 CD34+
cells/kg)

Exclusion Criteria:

- Active infection

- Pregnant woman are excluded from the study

- Subjects not using contraceptives are excluded from the study

- ANC ≤ 1,500/μL and/or platelet count ≤ 100,000/μL

- Life expectancy of ≤ 2 months

- Prior anti-B-cell radioimmunotherapy (e.g., Zevalin or Bexxar) [Patients who have
received prior anti-B-cell monoclonal antibody therapy (e.g., rituximab or
epratuzumab) will NOT be excluded.]

- Prior total body radiation therapy

- Positive human anti-mouse antibody (HAMA) testing