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

Non-Hodgkin's Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00434629
• Other study ID #: UPCC 18406
• Secondary ID: UPenn IRB#805353
• Status: Completed
• Phase: Phase 1
• First received: February 12, 2007
• Last updated: August 15, 2016
• Start date: February 2007
• Est. completion date: May 2015

Study information

• Verified date: August 2016
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• Bexxar
Day 0: Tositumomab, IV (in the vein) followed by test dose of 131I-Tositumomab, IV (in the vein) to determine treatment dose of 131I-Tositumomab. 1-2 weeks after Day 0: Tositumomab, IV (in the vein) followed by therapeutic dose 131I-Tositumomab (in the vein).

Locations

Country	Name	City	State
United States	Abramson Cancer Center, University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	dose-limiting toxicity		Week 7 after Bexxar	Yes
Primary	maximum tolerated dose		Week 7 after Bexxar	Yes
Secondary	overall response rate		Week 13 after Bexxar	No
Secondary	progression-free survival		5 years after Bexxar	No
Secondary	time to treatment failure		5 years after Bexxar	No