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

This study is currently recruiting participants.
Verified February 2014 by Baylor College of Medicine
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Houston Methodist Hospital
Information provided by (Responsible Party):
George Carrum, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01333046
First received: April 7, 2011
Last updated: February 17, 2014
Last verified: February 2014

April 7, 2011
February 17, 2014
January 2012
January 2018   (final data collection date for primary outcome measure)
Assessment of patients with adverse events [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
To determine the safety of 2 intravenous injections of autologous TAA-specific cytotoxic T-lymphocytes (CTL) in patients with Hodgkin's or non-Hodgkin's lymphoma.
IV injection of TAA-specific CTLs [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
To determine the safety of 2 intravenous injections of autologous TAA-specific cytotoxic T-lymphocytes (CTL) in patients with Hodgkin's or non-Hodgkin's lymphoma.
Complete list of historical versions of study NCT01333046 on ClinicalTrials.gov Archive Site
  • Obtain information on the expansion, persistence and anti-tumor effects of the adoptively-transferred TAA-specific CTL's [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Information on the expansion, persistence and anti-tumor effects of the adoptively transferred tumor-specific CTL 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 time point.
  • Assessment of increasing the spectrum of epitopes/antigens [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To determine whether CTL infusions increase the spectrum of epitopes/antigens targeted by endogenous T cells (epitope spreading).
  • Expansion, persistence and anti-tumor effects of TAA-specific CTLs [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To obtain information on the expansion, persistence and anti-tumor effects of the adoptively-transferred TAA-specific CTL in patients with Hodgkin's and non-Hodgkin's lymphoma
  • CTL infusions increasing the spectrum of epitopes/antigens [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To determine whether CTL infusions increase the spectrum of epitopes/antigens targeted by endogenous T cells (epitope spreading).
Not Provided
Not Provided
 
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

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 Lymphoma that show proof of infection 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 the 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 the tumor 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 if it is possible to direct these special T-lymphocytes 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 by 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.

The patient will give blood to make TAA specific cytotoxic T cells in the lab. These cells will be grown and frozen. The time from the collection of the blood to make the T cells to when the cells are given back to the patient is about 1 to 2 months.

The cells will then be injected by IV into the patient over 10 minutes. Initially, two doses of T cells will be given two weeks apart. The patient may be eligible to receive up to six additional doses of the T cells at 6-8 week intervals. All of the treatments will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital or Texas Children's Hospital.

There are 2 stages of this study: an antigen-escalation phase and a dose-escalation stage.

The antigen-Escalation phase will be first. Patients will receive TAA-specific T cells targeting first 1 and then 2 TAAs. Once this schedule proves safe, the next group of patients will receive TAA-specific T cells targeting first 2 and then 3 TAAs. This process will continue until all 4 levels are studied. This means that the final cohort of patients will receive TAA-specific T cells targeting first 4 and then 5 TAAs. If the side effects are too severe, the number of TAAs being targeted will be lowered or the T cell injections will be stopped.

After the antigen escalation phase the dose escalation phase will begin. Patients will be started on the lowest dose (1 of 4 different levels) of T cells. Once that dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 4 dose levels are studies. If the side effects are too severe, the dose will be lowered or the T cell injections will be stopped.

For both stages, patients will be followed after the injections up to one year from the last infusion.

Study Duration: Patients will be on study for approximately one year. If patients receive additional doses of the T cells as described above, the patient will be followed until 1 year after the last dose of T-cells.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
  • Hodgkin Disease
  • Biological: Antigen Escalation Stage

    Antigen Escalation Stage

    Each patient will receive 2 injections at the same dose (5x10^6 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

    Other Names:
    • T-cell injection
    • Tumor Specific CTL lines
  • Biological: Dose escalation study of T cells

    Dose Escalation Stage

    Four 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

    DL4:

    Day 0 and Day 14: 4 x 10^7 cells/m^2

    Other Name: TAA-CTL infusion
  • Experimental: Antigen Escalation Stage
    The first stage will be an "antigen escalation" stage using a fixed total dose of cells (5x10^6 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.
    Intervention: Biological: Antigen Escalation Stage
  • Experimental: Dose escalation study of T cells
    The second stage will be a dose escalation study, beginning with the same total dose of cells used in the antigen escalation phase (5x10^6 cells/m2 x 2). This second stage will evaluate the safety of T cells specific for all 5 tumor associated antigens.
    Intervention: Biological: Dose escalation study of T cells
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
January 2019
January 2018   (final data collection date for primary outcome measure)

Inclusion Criteria:

PROCUREMENT:

  1. Any patient, at least 18 years old regardless of sex with a diagnosis of Hodgkin's or non-Hodgkin's Lymphoma:

    - Group A:

    • 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 frontline therapy

    OR

    - Group B: After autologous or syngeneic SCT (as adjuvant therapy)

  2. Life expectancy of 6 weeks or greater.
  3. Hgb greater than 8.0
  4. Patient, parent/guardian able to give informed consent.

Inclusion Criteria:

TREATMENT:

  1. Any patient, at least 18 yrs old regardless of sex, with a diagnosis of Hodgkin's or non-Hodgkin's Lymphoma:

    Group A:

    • 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.

    OR

    - Group B: After autologous or syngeneic SCT (as adjuvant therapy)

  2. Life expectancy of 6 weeks or greater.
  3. Pulse oximetry of more than 95% on room air in patients who previously received radiation therapy
  4. Karnofsky/Lansky score of 50 or greater.
  5. Bilirubin 2x or less of upper limit of normal, AST 3x or less than the upper limit of normal, and Hgb >8.0
  6. Creatinine 2x or less of upper limit of normal for age.
  7. Patients should have been off other investigational therapy for one month prior to entry in this study.
  8. Patients should have been off conventional therapy for at least 1 week prior to entry in this study, including rituximab
  9. Patient able to give informed consent.
  10. Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom Females of child-bearing potential should use of at least two forms of contraception unless female has had a hysterectomy or tubal ligation.

Exclusion Criteria:

PROCUREMENT:

  1. Patients with severe intercurrent infection.
  2. Donors who are HIV positive at time of procurement. (test can be pending)

TREATMENT:

  1. Patients with severe intercurrent infection.
  2. Patients receiving systemic corticosteroids.
  3. Pregnant.
Both
Not Provided
No
Contact: George Carrum, MD 713-441-1450 gcarrum@bcm.edu
Contact: Ann Leen, PhD 832-824-4690 amleen@txch.org
United States
 
NCT01333046
H-27471-TACTAL, TACTAL
Yes
George Carrum, Baylor College of Medicine
Baylor College of Medicine
  • Center for Cell and Gene Therapy, Baylor College of Medicine
  • Texas Children's Hospital
  • Houston Methodist Hospital
  • National Cancer Institute (NCI)
Principal Investigator: Geoge Carrum, MD Baylor College of Medicine
Baylor College of Medicine
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP