A Pilot Study to Evaluate the Safety and Feasibility of Cellular Immunotherapy Using Genetically Modified Autologous CD20-Specific T Cells For Patients With Relapsed or Refractory Mantle Cell and Indolent B Cell Lymphomas
I. To assess the feasibility, safety and toxicity of cellular immunotherapy utilizing
ex-vivo expanded autologous T cells genetically modified to express a "second generation'
cluster of differentiation (CD)20-specific scFvFc:CD28:CD137:zeda chimeric immunoreceptor in
patients with recurrent or refractory CD20+ mantle cell or indolent lymphoma.
I. To determine the duration of in vivo persistence of adoptively transferred CD20-specific
T cells transfected with a CD20-specific scFvFc:CD28:CD137:zeda chimeric immunoreceptor.
II. To assess the trafficking of CD20-specific T cells to lymphoma masses. III. To evaluate
the development of host anti-CD20 scFvFc:CD28:CD137:zeda chimeric immunoreceptor and
anti-neomycin-resistance gene (NeoR) immune responses in study subjects.
CHEMOTHERAPY: Patients receive cyclophosphamide IV over 60 minutes.
IMMUNOTHERAPY: Beginning 2 days after completion of cyclophosphamide, patients receive
autologous CD20-specific T-cells IV over 30 minutes. Treatment repeats every 2-5 days for 3
MAINTENANCE THERAPY: Beginning 2 hours after the last T-cell infusion, patients receive
low-dose aldesleukin subcutaneously twice daily for 14 days.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Subjects who have achieved at least a partial remission lasting a minimum of 6 months may,
on a case-by-case basis, receive additional stored T cells following relapse.
After completion of study treatment, patients are followed up weekly for one month, monthly
for 1 year, and then annually for up to 2 years.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility of transfecting and expanding the necessary numbers of T cells and the types of problems and toxicities which might be encountered, graded according the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0
A true grade 3 or higher toxicity rate in excess of 20% attributed to T cell infusions will be considered grounds for stopping the study and amending the protocol to lower the cell infusion doses. If there ever exists sufficient evidence to suggest that the true T cell-related toxicity rate (grade 3 or higher, with the exception of fever > 40 degrees Celsius lasting less than 24 hours) exceeds 20%, the study will be stopped.
Up to 2 years after final T cell infusion
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|