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

NCT01333046 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: H-27471-TACTALTACTAL2P50CA126752-11
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief 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

Keywords

Hodgkin Lymphoma; Non-Hodgkin Lymphoma; CTL

Outcome Measures

Primary Outcomes (2)

• Assessment of patients with adverse events

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

  8 weeks

• Number of Patients with treatment related Serious Adverse Events

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

  8 weeks

Secondary Outcomes (2)

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

  1 year

• Assessment of increasing the spectrum of epitopes/antigens

  1 year

Study Arms (4)

Antigen-Escalation Stage

EXPERIMENTAL

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.

Biological: Antigen-Escalation Stage

Dose-Escalation Study Stage

EXPERIMENTAL

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.

Biological: Dose-Escalation Stage

azacytidine and multiTAA T cells Stage

EXPERIMENTAL

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).

Biological: azacytidine and multiTAA T cells Stage

Pediatric multiTAA T cells Stage

EXPERIMENTAL

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.

Biological: Pediatric multiTAA T cells Stage

Interventions

Antigen-Escalation Stage BIOLOGICAL

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

Also known as: T cell injection, Tumor-specific CTL lines

Antigen-Escalation Stage

Dose-Escalation Stage BIOLOGICAL

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

Also known as: TAA-CTL infusion

Dose-Escalation Study Stage

azacytidine and multiTAA T cells Stage BIOLOGICAL

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

azacytidine and multiTAA T cells Stage

Pediatric multiTAA T cells Stage BIOLOGICAL

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PROCUREMENT:
• Any patient regardless of sex, with a diagnosis of Hodgkin or non-Hodgkin lymphoma.
• Life expectancy of 6 weeks or greater.
• Hgb greater than or equal to 7.0
• Patient and,or parent,guardian able to give informed consent.
• TREATMENT:
• Any patient regardless of sex, with a diagnosis of Hodgkin or non-Hodgkin lymphoma:
• Group A: Patients greater than or equal to 18 years old
• with active disease:
• in second or subsequent relapse.
• in first relapse for indolent lymphoma after first-line therapy for relapse.
• or first relapse if immunosuppressive chemotherapy contraindicated.
• primary refractory disease or if persistent disease after first-line therapy of relapse.
• or multiply relapsed patients in remission who are at a high risk of relapse.
• or the lymphoma is a second malignancy e.g. a Richters transformation of CLL after failing front line therapy.

You may not qualify if:

• PROCUREMENT:
• Patients with severe intercurrent infection.
• Patients with active HIV infection at time of procurement (can be pending at the time of blood draw).
• Patients receiving systemic corticosteroids.
• TREATMENT:
• Patients with severe intercurrent infection.
• Patients receiving systemic corticosteroids.
• Pregnant breastfeeding.
• Active viral infection with HIV or hepatitis type B or C. "Active" infection defined as infectious disease testing indicating that patient blood is reactive for Hep B, C and/or HIV and confirmed using PCR to measure viral load.
• GROUP C (aza) Only:
• Abnormal coagulation parameters (PT greater than 15 seconds, PTT greater than 40 seconds, and/or INR greater than 1.5)
• Significant active cardiac disease within the previous 6 months including:
• NYHA class 4 CHF
• Unstable angina
• Myocardial infarction

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Vasileiou S, Lulla PD, Tzannou I, Watanabe A, Kuvalekar M, Callejas WL, Bilgi M, Wang T, Wu MJ, Kamble R, Ramos CA, Rouce RH, Zeng Z, Gee AP, Grilley BJ, Vera JF, Bollard CM, Brenner MK, Heslop HE, Rooney CM, Leen AM, Carrum G. T-Cell Therapy for Lymphoma Using Nonengineered Multiantigen-Targeted T Cells Is Safe and Produces Durable Clinical Effects. J Clin Oncol. 2021 May 1;39(13):1415-1425. doi: 10.1200/JCO.20.02224. Epub 2021 Jan 28.

  PMID: 33507803 DERIVED

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Geoge Carrum, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 7, 2011
• First Posted: April 11, 2011
• Study Start: January 1, 2012
• Primary Completion: September 27, 2021
• Study Completion (Estimated): September 27, 2027
• Last Updated: June 5, 2025

Record last verified: 2025-06

Locations

US (2)