Clinical trial NCT00434629: Safety and Efficacy of Bexxar Therapy in the Treatment of Relapsed/Residual B-Cell Lymphoma After Autologous Transplant
Official title: A Phase I Study of Bexxar® (Tositumomab and 131I-Tositumomab) Radioimmunotherapy in Patients With Relapsed or Residual CD20 Antigen-Expressing B-Cell Lymphomas Following Autologous Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-cell Lymphoma
Non-Hodgkin's Lymphoma
Keywords: lymphoma
Non-Hodgkin's lymphoma
B-cell lymphoma
Radioimmunotherapy
Bexxar
tositumomab
autologous hematopoietic stem cell transplantation
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2007-02-13
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients with B-cell lymphoma who relapse after autologous transplant tend to have a poor prognosis. Currently, there is no standard treatment for such patients. Bexxar is a radioactive antibody therapy that has shown a 60-80% response rate in non-transplanted patients with relapsed B-cell lymphoma. This study will test the safety and efficacy of Bexxar in the treatment of patients whose B-cell lymphoma has relapsed after an autologous transplant.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: dose-limiting toxicity
timeFrame: Week 7 after Bexxar
measure: maximum tolerated dose
timeFrame: Week 7 after Bexxar
Secondary outcomes:
measure: overall response rate
timeFrame: Week 13 after Bexxar
measure: progression-free survival
timeFrame: 5 years after Bexxar
measure: time to treatment failure
timeFrame: 5 years after Bexxar
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center, University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center, University of Pennsylvania
name: Stephen J. Schuster, MD
role: PRINCIPAL_INVESTIGATOR
References: