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

Summary

Patients have a type of lymph gland disease called Hodgkin or non-Hodgkin lymphoma which has come back, or may come back, or has not gone away after treatment, including the standard treatment known for these diseases. This a research study using special immune system cells called tumor associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental therapy.

This sort of therapy has been used previously to treat Hodgkin or non-Hodgkin lymphomas that show proof of infection with Epstein-Barr virus (EBV), the virus that causes infectious mononucleosis ("mono" or the "kissing disease"). EBV is found in cancer cells of up to half of all patients with Hodgkin's and non-Hodgkin lymphoma. This suggests that it may play a role in causing lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed. Investigators tested whether special white blood cells, called T cells, that were trained to kill EBV-infected cells could affect these tumors, and in many patients it was found that giving these trained T cells caused a complete or partial response.

However, many patients do not have EBV in their lymphoma cells; therefore investigators now want to test whether it is possible to direct these special T cells against other types of proteins on the tumor cell surface with similar promising results. The proteins that will be targeted in this study are called tumor associated antigens (TAAs) - these are cell proteins that are specific to the cancer cell, so they either do not show or show up in low quantities on normal human cells.

In this study, we will target five TAAs which commonly show on lymphoma, called: NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. This will be done by using special types of T cells called cytotoxic T lymphocytes (CTLs) generated in the lab.

In addition, some adult patients will receive a drug called azacytidine before giving the T cells. We hope that the combination helps the T cells work better.

Conditions

• Hodgkin Lymphoma
• Non-Hodgkin Lymphoma
• Hodgkin Disease

Interventions

BIOLOGICAL

Antigen-Escalation Stage

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

BIOLOGICAL

Dose-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

BIOLOGICAL

azacytidine and multiTAA T cells 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: 1. ANC \>1,000 or Platelets \>50,000 (or any other grade I AE attributable to aza) Adjustment: None 2. ANC 500-1000 or Platelets 25,000-50,000 (or any other grade II-III AE attributable to aza) Adjustment: 50% dose reduction 3. 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

BIOLOGICAL

Pediatric 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.

Sponsors & Collaborators

• Center for Cell and Gene Therapy, Baylor College of Medicine

  collaborator OTHER

• The Methodist Hospital Research Institute

  collaborator OTHER

• National Cancer Institute (NCI)

  collaborator NIH

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Geoge Carrum, MD · Baylor College of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-01-31

Primary Completion

2021-09-27

Completion

2027-09-27

FDA Drug

Yes

Countries

• United States

Study Locations