Clinical Trials /

TAA-Specific CTLS for Solid Tumors (TACTASOM)

NCT02239861

Description:

This is a clinical trial for patients with a solid tumor which has come back, or may come back, or has not gone away after treatment, including the standard treatment we know for these diseases. This is a study using special immune system cells called tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental therapy. The proteins that the investigators are targeting 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, the investigators target five common TAAs called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. On a different study, patients have been treated and so far this treatment has shown to be safe. The investigators now want to try this treatment in patients with solid tumors. This protocol is designed as a Phase I dose-escalation study.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

TAA-SPECIFIC CTLS FOR SOLID TUMORS (TACTASOM)

Title

  • Brief Title: TAA-SPECIFIC CTLS FOR SOLID TUMORS (TACTASOM)
  • Official Title: TUMOR-ASSOCIATED ANTIGEN (TAA)-SPECIFIC CYTOTOXIC T-LYMPHOCYTES ADMINISTERED TO PATIENTS WITH SOLID TUMORS
  • Clinical Trial IDs

    NCT ID: NCT02239861

    ORG ID: H-35425, TACTASOM

    Trial Conditions

    Bladder Cancer

    Breast Cancer

    Colorectal Cancer

    Endometrial Cancer

    Gastric Cancer

    Glioma/Medulloblastoma

    Head and Neck Cancer

    HCC

    Lung Cancer

    Melanoma

    Neuroblastoma

    Sarcoma (Osteo-, Synovial, Rhabdomyo-, Etc)

    Pancreatic Cancer

    Prostate Cancer

    Renal Cell Carcinoma

    Thyroid Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This is a clinical trial for patients with a solid tumor which has come back or may come
    back or has not gone away after treatment, including the standard treatment we know for
    these diseases. This is a study using special immune system cells called tumor associated
    antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental therapy.

    The proteins that the investigators are targeting 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 the
    investigators target five common TAAs called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. On a
    different study, patients have been treated and so far this treatment has shown to be safe.

    The investigators now want to try this treatment in patients with solid tumor.

    This protocol is designed as a phase I dose-escalation study.

    Detailed Description

    Blood will be collected from the patient and the TAA-specific CTLs will be made.

    The cells will be injected by IV into the patient over 10 minutes. The patient may be
    pretreated with acetaminophen (Tylenol) and diphenhydramine (Benadryl). Acetaminophen
    (Tylenol) and diphenhydramine (Benadryl) are given to prevent a possible allergic reaction
    to the T cell administration. Initially, two doses of T cells will be given two weeks apart.
    The patients disease will be assessed pre-infusion and then 6 weeks after the second
    infusion. If after the second infusion there is a reduction in the size of the patients
    tumor on CT or MRI scan as assessed by a radiologist, the patient can receive up to six (6)
    additional doses of the T cells at monthly intervals if they wish. All of the treatments
    will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital.

    In between the first and second T cell infusions and for 6 weeks after the last infusion,
    the investigators ask that the patient not receive any other anti-cancer treatments such as
    radiation therapy or chemotherapy. If the patient does receive any other therapies
    in-between the first and second infusion of T cells, they will be taken off treatment and
    will not be able to receive the second infusion of T cells.

    This is a dose escalation study. This means that at the beginning, 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 studied. If the side effects are too severe, the dose
    will be lowered or the T cell injections will be stopped.

    Medical tests before treatment:

    Physical exam Blood tests to measure blood cells, kidney and liver function Measurements of
    the patient's tumor by routine imaging studies. The investigators will use the imaging
    study that was used before to follow the patients tumor: Computer Tomogram (CT), Magnetic
    Resonance Imaging (MRI), or Positron Emission Tomography (PET) Pregnancy test if the patient
    is a female who can have children

    Medical tests during and after treatment:

    Blood tests to measure blood cells, kidney and liver function Imaging study 8 weeks after
    the 1st CTL infusion

    The investigators will follow the patient up to one year from their last infusion. To learn
    more about the way the T cells are working in the patient's body, an extra 20-40 mls (4-8
    teaspoons) of blood will be taken before and after each infusion, and at Weeks 1, 2, 4, and
    6. Afterwards, blood will be collected at 3, 6, 9, and 12 months after the last infusion.
    The investigators will use this blood to see how long the T cells last and to look at the
    immune response to the patient's response to cancer.

    Trial Arms

    Name Type Description Interventions
    TAA-specific CTLs Experimental Four different dosing schedules will be evaluated. Two to four patients will be evaluated on each dosing schedule. The first two patients on each dose level will be staggered by 4 weeks (which starts when the first infusion is given, day 0). The first patient on each dose level will be an adult. No subjects between the ages of 2-18 will be enrolled to a dose level on this protocol until the dose level has been shown to be safe in adults on the lymphoma protocol also being conducted under this same IND. Each patient will receive 2 injections at the same dose,14 days apart, according to the following dosing schedules: The expected volume of infusion will be 1 to 10 cc. Dose Level One: Day 0: 5 x 10^6 cells/m^2 Day 14: 5 x 10^6 cells/m^2 Dose Level Two: Day 0: 1 x 10^7 cells/m^2 Day 14: 1 x 10^7 cells/m^2 Dose Level Three: Day 0: 2 x 10^7 cells/m^2 Day 14: 2 x 10^7 cells/m^2 Dose Level Four: Day 0: 4 x 10^7 cells/m^2 Day 14: 4 x 10^7 cells/m^2

    Eligibility Criteria

    Procurement Inclusion Criteria

    1. Any patient regardless of sex with a solid tumor with expression of any of the
    following antigens (PRAME, SSX2, MAGEA4, NY-ESO1-1 and/or Survivin) with;

    1. Active disease after first line therapy;

    2. Refractory disease;

    3. As adjuvant therapy for high risk disease (high risk disease is a disease that
    has a > 50% risk of progression within 5 years)

    2. Patients with life expectancy at least 6 weeks.

    3. Age greater than or equal to 2 and less than or equal to 80 years old

    4. Hgb >8.0

    5. Patient able to give informed consent.

    Procurement Exclusion Criteria

    1. Patients with severe intercurrent infection.

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

    3. Patients in remission who are enrolled on another study where time to progression or
    disease free survival is a primary endpoint

    Treatment Inclusion Criteria

    1. Any patient regardless of sex with a solid tumor with expression of any of the
    following antigens (PRAME, SSX2, MAGEA4, NY-ESO1-1 and/or Survivin) with;

    1. Active disease after first line therapy;

    2. Refractory disease;

    3. As adjuvant therapy for high risk disease (high risk disease is a disease that
    has a > 50% risk of progression within 5 years)

    2. Patients with life expectancy at least 6 weeks.

    3. Age greater than or equal to 2 and less than or equal to 80 years old

    4. Pulse oximetry of >95% on room air in patients who previously received radiation
    therapy

    5. Patients with a Karnofsky/Lansky score of greater than or equal to 50

    6. Patients with bilirubin less than or equal to 2x upper limit of normal, AST less than
    or equal to 3x upper limit of normal, and Hgb >8.0

    7. Patients with a creatinine less than or equal to 2x upper limit of normal for age

    8. Patients should have been off other investigational therapy for one month prior to
    entry in this study.

    9. Patients should have been off conventional therapy for at least 1 week prior to entry
    in this study, including rituximab.

    10. Patient able to give informed consent.

    11. 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 must be willing to utilize one of the more effective birth control methods
    during the study unless female has had a hysterectomy or tubal ligation.

    Treatment Exclusion Criteria

    1. Patients with severe intercurrent infection.

    2. Patients receiving systemic corticosteroids (Patients off steroids for at least 48
    hours are eligible)

    3. Pregnant

    4. HIV positive

    5. Patients in remission who are enrolled on another study where time to progression or
    disease free survival is a primary endpoint

    Minimum Eligible Age: 2 Years

    Maximum Eligible Age: 80 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Number of patients with dose limiting toxicity

    Secondary Outcome Measures

    Number of patients with a disease response to the CTLs

    Persistence of the CTLs in the patient

    Expansion of the CTLs in the patient

    Trial Keywords

    Bladder cancer

    Breast cancer

    Colorectal cancer

    Endometrial cancer

    Gastric cancer

    Glioma/medulloblastoma

    Head and neck cancer

    HCC

    Lung cancer

    Melanoma

    Neuroblastoma

    Sarcoma (Osteo-, synovial, rhabdomyo-, etc)

    Pancreatic cancer

    Prostate cancer

    Renal cell carcinoma

    Thyroid cancer

    cytotoxic T lymphocytes