TAA-Specific CTL Therapy for Lymphoma
(TACTAL Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen byGeoge Carrum, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Baylor College of Medicine

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Research Team

Geoge Carrum, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults and children with Hodgkin or non-Hodgkin lymphoma that has returned after treatment, hasn't responded to treatment, or as a second cancer. Participants need a certain level of hemoglobin, normal organ function tests, and must not be pregnant. They should not have severe infections, HIV, hepatitis B/C infection or be on systemic steroids.

Inclusion Criteria

I have been diagnosed with Hodgkin or non-Hodgkin lymphoma.

PROCUREMENT: Life expectancy of 6 weeks or greater

PROCUREMENT: Patient and/or parent/guardian able to give informed consent

See 16 more

Exclusion Criteria

PROCUREMENT: Patients with active HIV infection at time of procurement (can be pending at the time of blood draw)

I am currently taking corticosteroids.

I am allergic to azacitidine or mannitol.

See 8 more

Treatment Details

Interventions

Antigen-Escalation Stage (CAR T-cell Therapy)
azacytidine and multiTAA T cells Stage (CAR T-cell Therapy)
Dose-Escalation Stage (CAR T-cell Therapy)
Pediatric multiTAA T cells Stage (CAR T-cell Therapy)

Trial OverviewThe study is testing TAA-specific cytotoxic T lymphocytes (CTLs), which are immune cells designed to target proteins commonly found on lymphoma cells. Some adult patients will also receive azacytidine before the CTLs to potentially enhance the effectiveness of the therapy.

Participant Groups

4Treatment groups

Experimental Treatment

Group I: azacytidine and multiTAA T cells StageExperimental Treatment1 Intervention

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).

Group II: Pediatric multiTAA T cells StageExperimental Treatment1 Intervention

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.

Group III: Dose-Escalation Study StageExperimental Treatment1 Intervention

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.

Group IV: Antigen-Escalation StageExperimental Treatment1 Intervention

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.