Clinical Trials /

CD19-Specific T-cells in Treating Patients With Advanced Lymphoid Malignancies

NCT02529813

Description:

This phase I clinical trial studies the side effects and best dose of CD19-specific T-cells in treating patients with lymphoid malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment. Sometimes researchers change the deoxyribonucleic acid (DNA) (genetic material in cells) of donated T-cells (white blood cells that support the immune system) using a process called "gene transfer." Gene transfer involves drawing blood from the patient, and then separating out the T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA, and then inject the changed T-cells into the body of the patient. Injecting modified T-cells made from the patient may help attack cancer cells in patients with advanced B-cell lymphoma or leukemia.

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Lymphoblastic Leukemia
  • Chronic Lymphocytic Leukemia
  • Non-Hodgkin Lymphoma
  • Small Lymphocytic Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CD19+ CAR T Cells for Lymphoid Malignancies
  • Official Title: CD19+ Chimeric Antigen Receptor T Cells for Patients With Advanced Lymphoid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 2013-1018
  • SECONDARY ID: NCI-2015-01492
  • NCT ID: NCT02529813

Conditions

  • Leukemia
  • Lymphoma

Interventions

DrugSynonymsArms
Fludarabine monophosphateFludarabine Phosphate, FludaraParticipant (Autologous)-Derived CAR T Cells
CyclophosphamideCytoxan, NeosarParticipant (Autologous)-Derived CAR T Cells

Purpose

Sometimes researchers change the DNA (genetic material in cells) of donated T-cells (white blood cells that support the immune system) using a process called "gene transfer." Gene transfer involves drawing blood from the patient, and then separating out the T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA, and then inject the changed T-cells into the body of the patient. The goal of this clinical research study is to find the highest tolerable dose of genetically changed T-cells that can be given to patients. Researchers want to learn if these genetically changed T-cells may be able to attack cancer cells in patients with advanced B-cell lymphoma or leukemia.

Detailed Description

      Study Groups:

      If you are found to be eligible to take part in this study, you will be assigned to a Dose
      Level of genetically changed T-cells based on when you begin to receive the cell product.

      Up to 4 dose levels of T-cells will be tested. Up to 3 participants will be enrolled at each
      dose level. The first group of participants will receive the lowest dose level. Each new
      group will receive a higher dose of than the group before it, if no intolerable side effects
      were seen. This will continue until the highest tolerable dose of T-cells is found.

      It will take about 7 weeks to modify and grow the necessary number of genetically changed
      T-cells in the lab.

      T Cell Collection for Treatment Arm 1:

      Within 30 days before the T-cell collection:

        -  You will have a physical exam.

        -  You will have a chest x-ray.

        -  You will have an electrocardiogram (EKG) to check your heart function.

        -  Blood (about 4 tablespoons) will be drawn for routine tests. Part of this blood sample
           will be used for a pregnancy test if you are able to become pregnant. To take part in
           this study, you must not be pregnant.

        -  HIV blood test. State law requires that the results of positive tests for HIV be
           reported to a local health agency.

        -  Mouse protein antibodies are used in the gene transfer process. If your body becomes
           immune to these proteins, your body may develop antibodies against the mouse antibodies
           (called "human anti-mouse antibodies" or HAMA). Part of the blood sample will be used
           to compare with another sample of blood collected after the gene transfer is complete
           to check for HAMA.

      Within 30 days after you have completed the screening tests, you may have leukapheresis
      performed at the Apheresis Clinic at MD Anderson. Before the leukapheresis:

        -  You will have a physical exam.

        -  Blood (about 4 tablespoons) will be drawn for routine tests and to measure levels of
           certain proteins.

      If you have leukapheresis performed to collect T-cells, the study doctor will discuss this
      procedure with you in more detail and you will be asked to sign a separate consent.

      If the doctor thinks it is in your best interest, instead of having leukapheresis, blood
      (about 13½ tablespoons) will be drawn to collect white blood cells.

      If not enough T cells can be collected, the leukapheresis or blood draw to collect white
      blood cells may be repeated.

      Chemotherapy:

      Before you receive the T cell infusion, you may receive standard chemotherapy
      (cyclophosphamide with or without fludarabine) by vein. The goal of this chemotherapy is to
      help the infused T-cells work better. If the doctor does not think it is in your best
      interest, you may not receive any chemotherapy. Your doctor will make this decision, and you
      will sign a separate consent for chemotherapy that will explain the drugs and their risks.

      Study Visits Before T-cell Infusion:

      Within 60 days before the T-cell infusions:

        -  Blood (about 2 tablespoons) will be drawn to check the status of the disease.

        -  You will have an echocardiogram (ECHO) or multigated acquisition (MUGA) scan to check
           your heart function.

        -  You will have lung function tests.

        -  If the study doctor thinks it is needed, you will have a bone marrow biopsy/aspiration
           to check the status of the disease. To collect a bone marrow biopsy/aspirate, an area
           of the hip or chest bone is numbed with anesthetic, and a small amount of bone and bone
           marrow is withdrawn through a large needle.

        -  If the study doctor thinks it is needed, you will have a lumbar puncture to check the
           status of the disease. To perform at lumbar puncture (also called a spinal tap), a
           special needle is inserted into the lower back through the space between the bones. The
           needle is used to withdraw a sample of the fluid that surrounds the spinal cord.

        -  If the study doctor thinks it is needed, you will have computed tomography (CT) scans
           and/or positron emission tomography (PET) scans to check the status of the disease.

      Within 7 days before starting chemotherapy (if you receive it):

        -  You will have a physical exam.

        -  Blood (about 2 tablespoons) will be drawn for routine tests. Part of this blood sample
           will be used for a pregnancy test if you are able to become pregnant.

        -  Blood (about 4 tablespoons) will be drawn to learn how your body's immune system
           responds to the T-cell infusion.

      T-cell Infusion:

      The T-cell infusion will be given by vein over about 15-30 minutes either all on one day or
      split into two days. It can be given up to 1 month after your last chemotherapy treatment.

      Before the infusion, you will receive drugs to lower your risk of allergic reaction to the
      T-cells. Tylenol (acetaminophen) will be given by mouth and Benadryl (diphenhydramine) may
      be given by mouth or by vein over a few minutes.

      Study Tests After T cell infusions:

      Within 3 days, 1 week (+/- 2 days), 2 weeks (+/- 3 days), 1 month (+/- 7 days), 3 months
      (+/- 7 days), 6 months (+/- 14 days), and 12 months (+/- 14 days) after the T-cell
      infusions, the following tests and procedures will be performed:

        -  You will have a physical exam.

        -  Blood (about 4 tablespoons) will be drawn for routine tests, tests to measure levels of
           certain proteins, and tests to check the status of the disease. Part of this blood
           sample will be used to compare against a sample of blood that was collected before the
           gene transfer to check for HAMA (6 months after the T-cell infusion only). If you leave
           the study early and the study doctor thinks it is possible, blood (about 2 teaspoons)
           will be drawn for HAMA testing at that time.

        -  Blood (about 4 tablespoons) will be drawn to learn how your body's immune system
           responds to the T-cell infusion (1, 3, 6, and 12 month timepoints only).

        -  Within 60 days of the T-cell infusion a test will be done to test your lung function
           (PFT's).

      At around 1, 3, 6, and 12 months after the last T-cell infusion, if the study doctor thinks
      it is needed, you will have CT scans and/or a bone marrow biopsy to check the status of the
      disease.

      Length of Study:

      Your participation on this study will be over after you have completed the last planned
      study visit about 12 months after the last T-cell infusion is complete. You may be taken off
      study early if the disease gets worse, if you cannot keep your appointments, if your doctor
      thinks it is in your best interest, if the cells cannot be manufactured or collected, or if
      you are unable to receive the T-cell infusion(s).

      Long-Term Follow-Up Study:

      For safety reasons, the U.S. Food and Drug Administration (FDA) requires that patients who
      receive stem cells infusions that have been treated with a gene transfer procedure must have
      long-term follow-up for at least 15 years after receiving the gene transfer. You will be
      asked to sign a separate consent form for a long-term follow-up study (Protocol 2006-0676).

      In the event of death due to any cause, an autopsy will be requested from your family if it
      is possible.

      This is an investigational study. The T-cell infusion using a gene transfer procedure is not
      commercially available or FDA approved. At this time, T-cell infusions using a gene transfer
      procedure are only being used in research.

      Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Participant (Autologous)-Derived CAR T CellsExperimentalParticipant (Autologous)-derived CAR T cells infused for active disease following lymphodepleting chemotherapy at discretion of treating physician. Three lymphodepletion regimens considered at discretion of treating physician. T-cell infusion given by vein either all on one day or split into two days. It can be given up to 1 month after last chemotherapy treatment.
  • Fludarabine monophosphate
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic
             leukemia, acute biphenotypic leukemia, Non-Hodgkin's Lymphoma, Small Lymphocytic
             Lymphoma, or Chronic Lymphocytic Leukemia with active disease defined by presence of
             >5% malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual
             disease by flow cytometry or molecular analysis for fusion proteins, and/or positive
             imaging for extramedullary disease. Patients must have measurable disease at time of
             study treatment.

          2. Confirmed history of CD19 positivity by flow cytometry for malignant cells.

          3. Lansky/Karnofsky Performance Scale > 60%.

          4. Patient able to provide written informed consent. Parent or guardian of minor patient
             able to provide written informed consent.

          5. Patient able to provide written informed consent for the long-term follow-up gene
             therapy study: 2006-0676. Parent or guardian of minor patient able to provide written
             informed consent for the long-term follow-up gene therapy study: 2006-0676.

          6. Age 1-80 years of age. Three adult patients will be treated before allowing treatment
             of children, as defined as younger than 18 years old.

        Exclusion Criteria:

          1. Positive beta HCG in female of child-bearing potential defined as not post-menopausal
             for 12 months or no previous surgical sterilization or lactating females.

          2. Patients with known allergy to bovine or murine products.

          3. Positive serology for HIV.

          4. Active hepatitis B or active hepatitis C.

          5. Has received DLI product within 6 weeks of CAR T cell infusion.

          6. Has received allogeneic hematopoietic stem cell transplant within 3 months of CAR T
             cell infusion; HSCT >3 months from CAR T cell infusion eligible.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) of Genetically Modified CD19-Specified T Cells
Time Frame:4 weeks
Safety Issue:
Description:Phase I study design developed by Ji et al.55 employed to find the MTD of CD19-specific T cell dose. MTD defined as highest dose for which the posterior probability of toxicity is closest to 25%. Dose limiting toxicity (DLT) defined as a new adverse event of grade 3 or higher involving cardiopulmonary, gastrointestinal, hepatic (excluding albumin), neurological, or renal CTC version 4 parameters that lasts for more than 3 days and that is probably or definitely related to the DLI within 30 days of infusion. Grade 3 or 4 GVHD occurring within 4 weeks of CAR T cell administration, unexplained neutropenia lasting more than 14 days, or graft failure following CAR T cell administration also considered DLT.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Leukemia
  • Lymphoma
  • Advanced Lymphoid Malignancies
  • CD19+ lymphoid malignancy
  • Multiple myeloma
  • MM
  • CD19-specific T cells
  • Chimeric Antigen Receptor T cells
  • CAR T cells
  • Autologous
  • Allogeneic
  • Fludarabine
  • Fludarabine phosphate
  • Cyclophosphamide
  • Cytoxan
  • Neosar
  • nonviral
  • non-viral
  • DNA plasmids

Last Updated

January 18, 2017