TAA-Specific CTLS for Solid Tumors (TACTASOM)
Condition: Rhabdomyosarcoma
MeSH terms: Rhabdomyosarcoma
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      Blood will be collected from the patient and TAA-specific CTLs will be made.

      The cells will be injected by IV into the patient over 1 - 10 minutes. The patient may be
      pre-treated with acetaminophen (Tylenol) and diphenhydramine (Benadryl). Acetaminophen
      (Tylenol) and diphenhydramine (Benadryl) are given to prevent a possible allergic reaction to
      the T cell infusion. Initially, two doses of T cells will be given two weeks apart. The
      patient's disease will be assessed pre-infusion and then 6 weeks after the second infusion.
      If after the second infusion, there is a reduction in size of the patient's tumor or if the
      tumor remains stable 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. All of the treatments
      will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital or Texas
      Children's 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, except PD1/PDL1 inhibitors as clinically indicated. 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:

      Before being treated, patients will receive a series of standard medical tests:

        -  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 previously performed to follow the patient's 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 TEST AFTER TREATMENT:

      Patients will receive standard medical test after infusion:

        -  Patients will receive standard medical test after infusion:

        -  Blood tests to measure blood cells, kidney and liver function.

        -  Imaging study 6 weeks after the 2nd CTL infusion.

      To learn more about the way the T cells are working in the patient's body, an extra 20-40 mL
      (4-8 teaspoons) of blood will be taken before 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. Patients will then be contacted once a year for
      up to 4 additional years (total of 5 years follow-up) to evaluate their disease response
      long-term.

      Study Duration: The patient's active participation in this study will last for approximately
      one (1) year. If the patient receives additional doses of the TAA-CTLs as described above,
      then the patient's active participation will last until one (1) year after his/her last dose.
      We will then contact the patient once a year for up to 4 additional years (total of 5 years
      follow-up) in order to evaluate his/her disease response long-term.
    

Intervention name(s): TAA-Specific CTLs
Intervention type(s): Biological
Intervention description(s): Patients may be pre-medicated with Benadryl up to 1 mg/kg IV (max 50 mg) and Tylenol 10 mg/kg po (max 650 mg).
Cell Administration: Tumor-specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line.
Patients with stable disease or better will receive up to 6 further doses of CTLs, as long as they continue to show disease stabilization or improvement by RECIST criteria at their 8 week or subsequent evaluations. Each dose will consist of the same number as their second injection or less (if there is not enough product available for the subject's original dose).
Patients will not be able to receive additional doses until the initial safety profile is completed at 6 weeks following the second infusion.
Other intervention name(s): Tumor Associated Antigen-Specific Cytotoxic T-Lymphocytes
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Rhabdomyosarcoma; cytotoxic T lymphocytes