This phase I trial is studying the side effects of giving genetically engineered lymphocytes
together with cyclophosphamide and aldesleukin in treating patients with relapsed or
refractory mantle cell lymphoma or indolent B-cell non-Hodgkin lymphoma. Placing a gene that
has been created in the laboratory into white blood cells may make the body build an immune
response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in
different ways to stop the growth of cancer cells, either by killing the cells or by
stopping them from dividing. Aldesleukin may stimulate the white blood cells to kill
lymphoma cells. Giving genetically engineered lymphocytes together with cyclophosphamide and
aldesleukin may be an effective treatment for mantle cell lymphoma and B-cell non-Hodgkin
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.
- Male or female subjects with immuno histopathologically documented CD20+ mantle cell
lymphoma, follicular non-Hodgkin lymphoma (NHL), small lymphocytic lymphoma/chronic
lymphocytic leukemia, marginal zone, or lymphoplasmacytic NHL of any age, gender, or
ethnic group who have relapsed or are refractory to conventional chemotherapy and who
are not eligible for Fred Hutchinson Cancer Research Center (FHCRC)/University of
Washington Medical Center (UWMC) transplant protocols (or who refuse participation in
- Willingness to sign an informed consent and undergo study tests
- Willingness to receive cytoreductive chemotherapy, if necessary to debulk tumors
prior to T cell administration, and to receive cyclophosphamide for lymphodepletion
- Serologic evidence of prior exposure to Epstein-Barr virus (EBV)
- Meets safety criteria to undergo leukapheresis
- Hemoglobin > 9.0 gm/dL
- White blood cell (WBC) > 2500 per microliter
- Alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x
Upper Limit of Normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =<
2.5 x Upper Limit of Normal
- Creatinine =< 1.6 mg/dL
- Willingness to use acceptable (barrier or hormonal methods) birth control as
appropriate during the course of the study
- Treatment with fludarabine or cladribine within the previous 2 years prior to
- Known central nervous system involvement with NHL
- Pulmonary involvement with NHL; a diagnosis of pulmonary lymphoma will be based in
part on findings from chest computed tomography (CT) and, if clinically appropriate,
- Exposure to chemotherapeutic agents (standard or experimental) or other
immunosuppressive therapies less than four weeks prior to apheresis; patients must
have recovered from acute side effects of such therapy
- Positive serology for human immunodeficiency virus (HIV)
- Active Hepatitis B or Hepatitis C infection
- History of hypersensitivity reactions to murine proteins or seropositivity for human
anti-mouse antibody (HAMA)
- Requirement for corticosteroid therapy during the study period unless used
specifically for amelioration of toxicity induced by transferred cells
- Treatment with anti-CD20 antibodies (rituximab, tositumomab, ibritumomab) within 4
months prior to start of T cell infusions
- Patients with lymph nodes in excess of 5 cm in diameter at time of T cell infusion
- Patients with > 5000 circulating CD20+ lymphocytes per mm^3 at time of T cell
- Previous allogeneic stem cell transplantation
- Life expectancy less than 90 days