Immune Consolidation With Activated T Cells Armed With OKT3 x Rituxan (Anti-CD3 x Anti-CD20) Bispecific Antibody (CD20Bi) After Peripheral Blood Stem Cell Transplant for High Risk CD20+ Non-Hodgkin's Lymphomas
- Determine the toxicity of high-dose combination chemotherapy comprising
cyclophosphamide, thiotepa, and carboplatin followed by autologous peripheral blood
stem cell transplantation and immunotherapy consolidation therapy comprising anti-CD3 x
anti-CD20 bispecific antibody (CD20Bi)-activated T cells (ATC) in patients with
- Determine the maximum tolerated dose of CD20Bi-ATC in patients treated with this
- Determine whether ATC traffic to tumor sites in select patients treated with this
- Assess the immune reconstitution of B cells and incidence of infection in patients
treated with this regimen.
- Compare relapse rates and overall survival of patients treated with this regimen with
OUTLINE: This is a dose-escalation study of activated T cells.
- Peripheral blood stem cell (PBSC) mobilization and collection: Patients receive
filgrastim (G-CSF) subcutaneously (SC) once daily for 5 days. They then undergo
leukaphereses to collect peripheral blood stem cells (PBSC). Some of the lymphocytes
are treated in the laboratory to produce anti-CD3 x anti-CD20 bispecific antibody
(CD20Bi)-activated T cells (ATC).
- High-dose chemotherapy and PBSC transplantation: Patients receive carmustine IV on day
-7, etoposide IV twice daily and cytarabine IV twice daily on days -6, -5, -4, and -3,
and melphalan IV on day -2. Autologous PBSC are reinfused on day 0.
- Immunotherapy consolidation: Patients receive immunotherapy consolidation comprising
CD20Bi-ATC IV over 15-30 minutes starting on day 4, once a week for 4 weeks for a total
of four infusions.
Cohorts of 3-6 patients receive escalating doses of CD20Bi-ATC until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
After completion of study treatment, patients are followed periodically for survival.
PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Lawrence G. Lum, MD, DSc
Barbara Ann Karmanos Cancer Institute
United States: Federal Government
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|
|Sinai-Grace Hospital||Detroit, Michigan 48235|