Clinical Trials /

Tumor-Associated Antigen-Specific Cytotoxic T-Lymphocytes for Multiple Myeloma

NCT02291848

Description:

This study is for patients that have a cancer called Multiple Myeloma. This research study uses special immune system cells called tumor associated antigen (TAA)-specific cytotoxic T lymphocytes (CTLs), a new experimental therapy. The proteins that investigators are targeting in this study are called tumor associated antigens (TAAs). These are cell proteins that are specific to the cancer cell.They either do not show or show up in low quantities on normal human cells. In this study we target five common TAAs called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. On a different protocol, patients have been treated and so far this treatment has shown to be safe. Investigators now want to try this treatment in patients with multiple myeloma. These TAA-specific CTLs are an investigational product not approved by the Food and Drug Administration. The purpose of this study is to find the largest safe dose of TAA-specific CTLs, to learn what the side effects are, and to see whether this therapy might help patients with multiple myeloma.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Tumor-Associated Antigen-Specific Cytotoxic T-Lymphocytes for Multiple Myeloma
  • Official Title: Administration of Tumor-Associated Antigen (TAA)-Specific Cytotoxic T-Lymphocytes to Patients With Active Myeloma (TACTAM)

Clinical Trial IDs

  • ORG STUDY ID: H-35626, TACTAM
  • NCT ID: NCT02291848

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
TAA-specific CTLsGroup A

Purpose

This study is for patients that have a cancer called Multiple Myeloma. This research study uses special immune system cells called tumor associated antigen (TAA)-specific cytotoxic T lymphocytes (CTLs), a new experimental therapy. The proteins that investigators are targeting in this study are called tumor associated antigens (TAAs). These are cell proteins that are specific to the cancer cell.They either do not show or show up in low quantities on normal human cells. In this study we target five common TAAs called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX. On a different protocol, patients have been treated and so far this treatment has shown to be safe. Investigators now want to try this treatment in patients with multiple myeloma. These TAA-specific CTLs are an investigational product not approved by the Food and Drug Administration. The purpose of this study is to find the largest safe dose of TAA-specific CTLs, to learn what the side effects are, and to see whether this therapy might help patients with multiple myeloma.

Detailed Description

      Up to 390 mL (78 teaspoons) of blood will be collected from the patient on one to three
      occasions over a two month period. Under certain conditions related to the patient's health,
      the blood may need to be collected using a process called apheresis. Apheresis is the process
      where blood is passed through a machine that separates out the components of the blood that
      is needed. The remainder of the blood is then returned to the patient's body.

      Investigators will use this blood to grow T cells. They will first grow a special type of
      cells called dendritic cells which will cause activity in the T cells. Once these are made
      the investigator will load them with small pieces of protein called peptides taken from the
      TAAs that they want to target. This helps to train the T cells to kill cells with TAAs on
      their surface. Then the investigators expand these TAA-specific CTLs.

      The cells will be infused by intravenous (IV) infusion into the patient over 10 minutes. The
      patient may be pre-treated with acetaminophen (Tylenol) and diphenhydramine (Benadryl).
      Initially, two doses of TAA-specific CTLs 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 decrease in the patient's disease or it remains stable, the
      patient can receive up to six (6) additional doses of the TAA-specific CTLs at monthly
      intervals. 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 infusions and for 6 weeks after the last infusion, the
      patient is asked not to receive any other anti-cancer treatments, such as radiation therapy
      or chemotherapy, with the exception of lenalidomide, thalidomide, pomalidomide, or immune
      checkpoint inhibitors, such as CTLA4 and/or PD-1/PD-L1 inhibitors. If they do receive any
      other therapies in-between the first and second infusion of cells, the patient will be taken
      off treatment and will not be able to receive the second infusion of cells.

      This is a dose escalation study. This means that at the beginning, patients will be started
      on the lowest dose (1 of 3 different levels) of TAA-specific CTLs. Once that dose schedule
      proves safe, the next group of patients will be started at a higher dose. This process will
      continue until all 3 dose levels are studied. If the side-effects are too severe, the dose
      will be lowered or the TAA-specific CTL infusions will be stopped.

      Medical Tests Before Treatment

      Before being treated, the patient will receive a series of standard medical tests:

        -  Physical exam.

        -  Blood tests to measure blood cells, kidney and liver function.

        -  Measurement of the patient's multiple myeloma by blood tests and bone marrow biopsy
           (within 4 weeks before the CTL infusion)

        -  Measurements of the patient's tumor by routine imaging studies. We will use the imaging
           study that was used before to follow the patient's tumor: Computerized Tomography (CT),
           Magnetic Resonance Imaging (MRI), or Positron Emission Tomography (PET/CT), skeletal
           bone survey. These studies will be done on a case-by-case basis at the descretion of the
           patient's treating physician.

        -  Pregnancy test (using a blood sample) if the patient is a female who can have children.

      Medical Tests After Treatment:

      Patients will receive standard medical tests after their infusion:

        -  Blood tests to measure blood cells, kidney and liver function.

        -  Measurement of the patient's multiple myeloma by blood tests and bone marrow biopsy (at
           4-6 weeks and 8-12 weeks post 1st CTL infusion).

      To learn more about the way the TAA-specific CTLs 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 TAA-specific CTLs last, and to look
      at the immune response to the 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.
    

Trial Arms

NameTypeDescriptionInterventions
Group AExperimentalPatients receiving TAA-specific CTLs as therapy for Myeloma
  • TAA-specific CTLs
Group BExperimentalPatients receiving TAA-Specific CTLs as adjunctive therapy following autologous or syngeneic transplant for myeloma
  • TAA-specific CTLs

Eligibility Criteria

        Procurement Inclusion Criteria

          -  Any patient, at least 18 yrs old regardless of sex, with a diagnosis of Myeloma after
             receiving at least one treatment regimen.

          -  Patients with life expectancy greater than or equal to 6 weeks.

          -  Hgb greater than or equal to 7.0 (transfusions allowed).

          -  Patient able to give informed consent.

        Treatment Inclusion Criteria

        - Any patient, at least 18 yrs old regardless of sex, with a diagnosis of Myeloma after
        receiving at least one treatment regimen. If patient has received an autologous or
        syngeneic SCT they must be >90 days post-transplant (Group A) OR

        Following autologous or syngeneic SCT (as adjuvant therapy) and <90 days post transplant
        (Group B)

          -  Patients with life expectancy greater than or equal to 6 weeks.

          -  Pulse oximetry of >93% on room air in patients who previously received radiation
             therapy.

          -  Patients with a Karnofsky score of greater than or equal to 50.

          -  Patients with bilirubin less than or equal to 2 times upper limit of normal, AST less
             than or equal to 3 times upper limit of normal, and Hgb greater than or equal to 7.0
             (transfusion allowed).

          -  Engrafted post transplant (ANC >500) and ANC >500 at the time of infusion.

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

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

          -  Patients should have been off conventional therapy for at least 48 hours prior to
             entry in this study (except for lenalidomide, thalidomide, pomalidomide or immune
             checkpoint inhibitors such as CTLA4 and/or PD-1/PD-L1 inhibitors)

          -  Patient able to give informed consent.

          -  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.

        Procurement Exclusion Criteria

          -  Patients with severe active infection.

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

        Treatment Exclusion Criteria

          -  Patients with severe active infection.

          -  Patients receiving systemic corticosteroid within 48 hours of CTL infusion.

          -  Pregnant or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Patients with Adverse events
Time Frame:8 weeks
Safety Issue:
Description:To determine the safety of 2 intravenous injections of autologous TAA-specific cytotoxic T-lymphocytes (CTL) in patients with Myeloma.

Secondary Outcome Measures

Measure:Expansion of the CTLs
Time Frame:1 year
Safety Issue:
Description:Information on the expansion 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.
Measure:Persistence of the CTLs
Time Frame:1 year
Safety Issue:
Description:Information on the persistence 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.
Measure:Reduction of the Multiple Myeloma
Time Frame:8 weeks
Safety Issue:
Description:Comparison of diagnostic imaging studies from pre-infusion to 6 weeks following the second infusion will be summarized. Frequencies and proportions of responders will be summarized overall and by dose levels if there are enough patients per dose level.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Baylor College of Medicine

Trial Keywords

  • Multiple Myeloma
  • Cytotoxic T-lymphocytes

Last Updated

January 17, 2020