(TAA)-Specific Cytotoxic T-Lymphocytes to Pediatric Patients With Lymphomas (pediTACTAL).

NCT05134740 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: H-49884 (pediTACTAL)
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators have previously used this sort of therapy to treat Hodgkin or non-Hodgkin lymphoma that is associated with the virus that causes infectious mononucleosis ("mono" or the "kissing disease"), Epstein-Barr virus (EBV). 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 previously tested special white blood cells (cells that help the body fight disease and infection), called T cells. The T cells were trained to kill EBV-infected cells and were tested to see whether treatment with these cells could affect these tumors. In many patients investigators found that giving these trained T cells caused a complete or partial response. However, many patients do not have EBV found in their lymphoma cells. Therefore, investigators now want to test whether special T lymphocytes directed against other types of proteins that show on the tumor cell surface can result in 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 stage of the study, investigators will target five TAAs which commonly show on lymphoma cells , called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. Investigators will do this by using special types of T cells called cytotoxic T lymphocytes (CTLs) generated in the lab. These TM-specific T cells are an investigational product not yet approved by the U.S. Food and Drug Administration. The purpose of this stage of the study is to find out if TM-specific cytotoxic T cells are safe in children. The investigators want to learn what the side-effects are, and to see whether this therapy might help treat patients who are considered high risk for relapse of Hodgkin disease or non-Hodgkin lymphoma.

Conditions

Hodgkins Lymphoma; Non Hodgkins Lymphoma

Keywords

Hodgkins Lymphoma; Non Hodgkins Lymphoma; TAA; TAA specific T lymphocytes; Hodgkins Lymphona high risk for relapse; Non-Hodgkin's Lymphoma high risk for relapse; pediatric Hodgkin's Lymphoma high risk; pediatric non-Hodgkin's Lymphoma high risk

Outcome Measures

Primary Outcomes (1)

• Treatment-related adverse event (tAE) Rate

  Treatment-related adverse event (tAE) rate is the proportion of participants with tAE measured by the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The tAE will be defined as development of Grade III-IV events in any organ system that do not return to grade I within 72 hours with the exception of events that are clearly unrelated, and, of hematological toxicities, which are only considered a tAE if Grade III persisting for up to 10 days or greater than or equal to Grade IV. In addition grade 2 or greater autoimmune reaction will be considered a tAE.

  8 weeks post first CTL infusion

Secondary Outcomes (1)

• Obtain information on the expansion, persistence and anti-tumor effects of the adoptively-transferred TAA-specific CTLs

  8 weeks

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Patients receiving autologous TAA-specific cytotoxic CTLs

Biological: TAA-specific CTLs

Interventions

TAA-specific CTLs BIOLOGICAL

Each patient will receive 2 infusions at the same dose, 14 days apart, according to the following dose level: 2 x 10\^7/m2

Experimental Arm

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Any pediatric patient (age ≥ 1 year and ≤ 21 years), regardless of sex, with a diagnosis of Hodgkin or non-Hodgkin Lymphoma.
• Patients with life expectancy \> 6 weeks.
• Hgb ≥ 7.0 (transfusions allowed).
• Informed Consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. If applicable, patient assents to procurement,

You may not qualify if:

• Patients with severe intercurrent infection.
• Patients with active HIV, Hepatitis B, or Hepatitis C infection at time of procurement (can be pending at the time of blood draw).
• Patients receiving systemic corticosteroids at the time of or within one week prior to procurement.
• Presence of grade 2-4 acute GVHD or active chronic GVHD \> mild global severity score.
• Any pediatric patient (age ≥ 1 year and ≤ 21 years), regardless of sex, with a diagnosis of Hodgkin or non-Hodgkin Lymphoma who are in complete remission (CR), but at high risk for relapse (specifically, who are stage 3 or stage 4 at diagnosis, are in second complete remission (CR2), and who have previously received \>2 lines of lymphoma-directed therapy).
• Pulse oximetry of \> 90% on room air in patients who previously received radiation therapy.
• Patients with a Karnofsky/Lansky score of \> 60
• Patients with bilirubin \< 3x upper limit of normal
• Patients with a creatinine ≤ 2x upper limit of normal for age.
• Patients with AST \< 3x upper limit of normal.
• Patients with Hgb ≥ 7.0 (transfusions allowed)
• Acceptable organ function based on clinical or laboratory findings according to investigator discretion
• Patients should have been off other investigational therapy for one month prior to entry in this study.
• Patients should have been off conventional therapy including rituximab for at least 1 week prior to entry in this study, and at least 4 weeks since last dose of radiation (if applicable)
• Informed Consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. If applicable, patient assents to participation in trial.

Sponsors & Collaborators

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

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Lauren Scherer, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Instructor

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: November 26, 2021
• Study Start: April 1, 2024
• Primary Completion: February 24, 2025
• Study Completion (Estimated): February 1, 2030
• Last Updated: October 22, 2024

Record last verified: 2024-10

Locations

US (1)