Trial record 9 of 35 for:    mononucleosis

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Baylor College of Medicine
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
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
  Purpose

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.


Condition Intervention Phase
Hodgkin Lymphoma
Non-Hodgkin Lymphoma
Hodgkin Disease
Biological: Antigen Escalation Stage
Biological: Dose escalation study of T cells
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Administration of Tumor-Associated Antigen (TAA)-Specific Cytotoxic T-Lymphocytes to Patients With Active or Relapsed Hodgkin or Non-Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Estimated Enrollment: 60
Study Start Date: January 2012
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01333046

Contacts
Contact: George Carrum, MD 713-441-1450 gcarrum@bcm.edu
Contact: Ann Leen, PhD 832-824-4690 amleen@txch.org

Locations
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: George Carrum, MD    713-441-1450    gcarrum@bcm.edu   
Contact: Ann Leen, PhD    832-824-4690    amleen@txch.org   
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: George Carrum, MD    713-441-1450    gcarrum@bcm.edu   
Contact: Ann Leen, PhD    832-824-4690    amleen@txch.org   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Investigators
Principal Investigator: Geoge Carrum, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: George Carrum, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01333046     History of Changes
Obsolete Identifiers: NCT01556269
Other Study ID Numbers: H-27471-TACTAL, TACTAL
Study First Received: April 7, 2011
Last Updated: February 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
Hodgkin Lymphoma
Non-Hodgkin Lymphoma
CTL

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 28, 2014