T-Lymphocytes in Treating Patients With Active or Relapsed Hodgkin Lymphoma or Non-Hodgkin Lymphoma

OBJECTIVES:

- To determine the safety of 2 intravenous injections of autologous tumor-associated
antigen (TAA)-specific cytotoxic T-lymphocytes (CTL) in patients with Hodgkin (HL) or
non-Hodgkin lymphoma (NHL).

- To determine whether infusion of TAA-specific T cells targeting multiple tumor antigens
has a safety profile similar to the adoptive transfer of single antigen-targeted T
cells.

- To obtain information on the expansion, persistence, and anti-tumor effects of the
adoptively transferred TAA-specific CTL in patients with HL or NHL.

- To determine whether CTL infusions increase the spectrum of epitopes/antigens targeted
by endogenous T cells (epitope spreading).

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to
cytotoxic T-lymphocytes (CTLs) treatment (as therapy for HL or NHL [Group A] vs adjunctive
therapy following autologous or syngeneic transplantation [Group B]).

Patients undergo peripheral blood mononuclear cells collection for cytoxic T-cell
lymphocytes (CTLs) generation. T cells are stimulated with antigen-presenting cells,
dendritic cells (DC) pulsed with pepmixes spanning the tumor-associated antigens SSX2,
MAGEA4, Survivin, PRAME, and NY-ESO-1 in the presence of pro-proliferative cytokines
interleukin (IL)-7, IL-12, IL-15, and IL-6 . Cells are then expanded in the presence of
IL-2.

Antigen-escalation stage: Patients receive autologous tumor-associated antigen
(TAA)-specific CTLs IV over 10 minutes on days 0 (PRAME- and SSX-specific T cells) and 28
(PRAME/SSX/MAGE/NY-ESO-specific T cells) in the absence of disease progression or
unacceptable toxicity.

Dose-escalation stage: Patients receive autologous TAA-specific CTLs IV over 10 minutes on
days 0 (PRAME- and SSX-specific T cells) and 14 (PRAME/SSX/MAGE/NY-ESO-specific T cells).
Patients with stable disease or responsive disease (partial response) receive up to 3
courses (6 doses) every 6 weeks in the absence of disease progression or unacceptable
toxicity.

After completion of treatment, patients are followed up every 2 weeks for 8 weeks and then
at 3, 6, 9, and 12 months.

DISEASE CHARACTERISTICS:

- Diagnosis of Hodgkin or non-Hodgkin lymphoma meeting one of the following criteria:

- Group A: With active disease meeting one of the following criteria:

- In second or subsequent relapse

- In first relapse for indolent lymphoma after first-line therapy for relapse

- In first relapse if immunosuppressive chemotherapy contraindicated

- Primary refractory disease or if persistent disease after first-line
therapy of relapse

- Multiply relapsed patients in remission who are at a high risk of relapse

- The lymphoma is a second malignancy (e.g., a Richters transformation of
chronic lymphocytic leukemia [CLL] after failing front-line therapy)

- Group B: After autologous or syngeneic stem cell transplantation (SCT)(as
adjuvant therapy)

PATIENT CHARACTERISTICS:

- Patients with life expectancy ≥ 6 weeks

- Hemoglobin (Hgb) > 8.0 g/dL (transfusions allowed)

- No patients with severe intercurrent infection

- No patients who are human immunodeficiency virus (HIV) positive at time of
procurement

- Karnofsky/Lansky score of ≥ 50%

- Bilirubin ≤ 2 times upper limit of normal (ULN)

- Aspartate aminotransferase (AST) ≤ 3 times ULN

- Creatinine ≤ 2 times ULN for age

- Pregnant women are excluded from this research; the male partner should use a condom;
females of child-bearing potential should use at least two forms of contraception
unless patient has had a hysterectomy or tubal ligation

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Patients should have been off other investigational therapy for one month prior to
entry in this study

- Patients should have been off conventional therapy for at least 1 week prior to entry
in this study

- No patients receiving systemic corticosteroids