The first stage will be an "antigen-escalation" stage using a fixed total dose of cells (5 x 10^6 cells/m^2 x 2) to evaluate the safety of the T cells primed against PRAME pepmix, and then SSX pepmix, and then MAGE A4 pepmix, and then NY-ESO pepmix, and then SURVIVIN pepmix.

In the dose escalation stage, three dose levels will be studied. Patients in the dose escalation portion of the study will be entered and stratified separately to the following two groups:
Group A: Patients receiving CTLs as therapy for Hodgkin's or non-Hodgkin's lymphoma.
Group B: Patients receiving CTLs as adjunctive therapy following autologous or syngeneic transplant.

This phase will administer aza intravenously at a dose of 75 mg/m2 after premedication with an anti-emetic such as ondansetron po or IV (up to a maximum dose of 16 mg ondansetron or equivalent). This phase will determine whether infusion of TAA-specific T cells (at dose level 2 - 1x10^7) targeting multiple tumor antigens in combination with azacytidine is safe, and whether CTL infusions (with or without azacytidine) increase the spectrum of epitopes/antigens targeted by endogenous T cells (epitope spreading).

This phase will give patients < 18 years old two infusions (on Day 0 and Day 14) of multi-TAA specific T cells at a fixed dose of 1x10^7 cells/m2. This phase will test the safety and efficacy of multiTAA-specific T cells in pediatric patients with active HL/NHL.

Hodgkin Lymphoma

Non-Hodgkin Lymphoma

Hodgkin Disease

Antigen-Escalation Stage
Each patient will receive 2 injections at the same dose (5 x 10^6 cells/m2), 28 days apart, according to the following schedules:
Schedule One:
Day 0: PRAME-specific T cells
Day 28: PRAME- and SSX-specific T cells
Schedule Two:
Day 0: PRAME- and SSX-specific T cells
Day 28: PRAME/SSX/MAGE-specific T cells
Schedule Three:
Day 0: PRAME/SSX/MAGE-specific T cells
Day 28: PRAME/SSX/MAGE/NY-ESO specific T cells
Schedule Four:
Day 0: PRAME/SSX/MAGE/NY-ESO specific T cells
Day 28: PRAME/SSX/MAGE/NY-ESO/Survivin-specific T cells

Antigen-Escalation Stage

Dose-Escalation Stage
Three different dosing schedules will be evaluated. Each patient will receive 2 injections at the same dose, 14 days apart, according to the following dosing schedules:
DL1: Day 0 and Day 14: 5 x 10^6 cells/m^2
DL2: Day 0 and Day 14: 1 x 10^7 cells/m^2
DL3: Day 0 and Day 14: 2 x 10^7 cells/m^2

Dose-Escalation Stage

Up to 15 patients will be treated with 3 cycles of aza at a dose of 75 mg/m2 I.V. administered for 5 days/cycle followed, within 28 days of the last aza dose, by two infusions (on Day 0 and Day 14) of multi-TAA specific CTLs at a fixed dose of 1x10^7 cells/m2. If drug-related myelosuppression occurs aza dosing will be modified, according to the following:
ANC >1,000 or Platelets >50,000 (or any other grade I AE attributable to aza)
Adjustment: None
ANC 500-1000 or Platelets 25,000-50,000 (or any other grade II-III AE attributable to aza)
Adjustment: 50% dose reduction
ANC <500 or any episode of febrile neutropenia or platelets <25,000 or any episode of bleeding attributed to thrombocytopenia (or any other grade IV or higher AE attributable to aza)
Adjustment: Discontinue drug, can proceed with CTL infusion if eligible within 28 days of last aza infusion

azacytidine and multiTAA T cells Stage

Patients < 18 years old will receive two infusions (on Day 0 and Day 14) of multi-TAA specific T cells at a fixed dose of 1x10^7 cells/m2. We will enroll and infuse at least 5 adolescents on the pediatric arm before opening to all patients.

Pediatric multiTAA T cells Stage

Houston Methodist Hospital

Texas Children's Hospital

Administration of TAA-Specific CTLs; Hodgkin or Non-Hodgkin Lymphoma; TACTAL

Administration of Tumor-Associated Antigen (TAA)-Specific Cytotoxic T-Lymphocytes to Patients With Active or Relapsed Hodgkin or Non-Hodgkin Lymphoma

To determine the safety of 2 intravenous injections of autologous TAA-specific cytotoxic T lymphocytes (CTLs) in patients with Hodgkin or non-Hodgkin lymphoma.

To determine whether infusion of TAA-specific T cells targeting multiple tumor antigens in combination with azacytidine is safe

Information on the expansion, persistence and anti-tumor effects of the adoptively transferred tumor-specific CTLs will be analyzed for the immunological parameters based on multimer analysis, intracellular cytokine staining and ELIspot assays to assess the frequency of cells secreting γ-IFN using the descriptive statistics such as mean, median, standard deviation at each timepoint.

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

George Carrum

Associate Professor

Baylor College of Medicine

Center for Cell and Gene Therapy, Baylor College of Medicine

The Methodist Hospital System

National Cancer Institute (NCI)

Hodgkins Lymphoma

1 injection One of the following 4 dose levels: 2x 10^7 cells/m2, 1x 10^8 cells/m2, 3 x 10^8 cells/m2, 1 x 10^9 cells/m2

LMP1 SPECIFIC CYTOTOXIC T-LYMPHOCYTES

LMP2-SPECIFIC CYTOTOXIC T-LYMPHOCYTES

The Methodist Hospital

Lmp1 and Lmp2 Specific CTLs Following Cd45 Antibody for Relapsed Ebv-Positive Hodgkin's Or Non-Hodgkin's Lymphoma

Administration of LMP1- and LMP2- Specific Cytotoxic T-Lymphocytes Following CD45 Antibody to Patients With Relapsed EBV-Positive Hodgkin's or Non-Hodgkin's Lymphoma or Chronic Active EBV Infection (ALDI)

infectious mononucleosis/erbrechen

Administration of TAA-Specific CTLs; Hodgkin or Non-Hodgkin Lymphoma; TACTAL

Lmp1 and Lmp2 Specific CTLs Following Cd45 Antibody for Relapsed Ebv-Positive Hodgkin's Or Non-Hodgkin's Lymphoma

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