Clinical Trials /

CD30 CAR T Cells, Relapsed CD30 Expressing Lymphoma (RELY-30)

NCT02917083

Description:

The subject has a type of lymph gland cancer called Lymphoma. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers; they both have shown promise, but have not been strong enough to cure most patients. Investigators hope that both will work better together. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. They now want to test whether these genetically modified T cells given after chemotherapy will be more effective at killing cancer cells. The gene that will be put into the T cells makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric receptor-activated T cells (CD30.CAR T cells) seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are unknown. Several studies suggest that the infused T cells need room to be able to multiply and grow to accomplish their functions, and that this may not happen if there are too many other T cells in circulation. Because of that, doctors may use chemotherapy drugs to decrease the level of circulating T cells prior to the CD30.CAR T cells infusion. This is called "lymphodepletion". CD30.CAR T cells have previously been studied in lymphoma patients. What is new for this study is that lymphodepletion chemotherapy will be administered in patients who are not post autologous transplant in the hope that it will result in more durable anti-tumor effects.

Related Conditions:
  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CD30 CAR T Cells, Relapsed CD30 Expressing Lymphoma (RELY-30)
  • Official Title: Phase I Study of Relapsed CD30 Expressing Lymphoma Treated With CD30 CAR T Cells (RELY-30)

Clinical Trial IDs

  • ORG STUDY ID: H-37966, RELY-30
  • SECONDARY ID: RELY-30
  • NCT ID: NCT02917083

Conditions

  • Hodgkin's Lymphoma
  • Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
CyclophosphamideCytoxanCD30.CAR T Cells
FludarabineFludaraCD30.CAR T Cells

Purpose

The subject has a type of lymph gland cancer called Lymphoma. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers; they both have shown promise, but have not been strong enough to cure most patients. Investigators hope that both will work better together. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. They now want to test whether these genetically modified T cells given after chemotherapy will be more effective at killing cancer cells. The gene that will be put into the T cells makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric receptor-activated T cells (CD30.CAR T cells) seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are unknown. Several studies suggest that the infused T cells need room to be able to multiply and grow to accomplish their functions, and that this may not happen if there are too many other T cells in circulation. Because of that, doctors may use chemotherapy drugs to decrease the level of circulating T cells prior to the CD30.CAR T cells infusion. This is called "lymphodepletion". CD30.CAR T cells have previously been studied in lymphoma patients. What is new for this study is that lymphodepletion chemotherapy will be administered in patients who are not post autologous transplant in the hope that it will result in more durable anti-tumor effects.

Detailed Description

      To prepare the CD30.CAR T cells, research staff will take some blood from the subject. This
      would be drawn as two separate blood collections.

      Alternatively, if the subject's blood counts are low, staff may collect the cells needed to
      prepare T cells by a pheresis procedure. This procedure will involve placing a needle in both
      arms, collecting the cells over 3 to 6 hours during which the subject will be required to lie
      relatively still.

      After the T cells have been collected, some of them will be activated stimulating them with
      antibodies and will then be infected with a retroviral vector (a special virus that can
      carries a new gene into cells) containing a new gene called anti-CD30 that will make an
      antibody to lymphoma cells. The trained cells are called CD30.CAR T cells. Then, the cells
      will be tested to make sure that they kill lymphoma cells that express the CD30 antigen and
      not normal cells.

      The cells generated will be frozen and stored to give back to the subject.

      This is a dose escalation study. This means that at the beginning, patients will be started
      on the lowest doses (1 of 3 different levels) of CD30.CAR 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 3 dose levels are studied. If the side effects are too severe, the dose
      will be lowered or the T cell infusions will be stopped. The risks of harm and discomfort
      from the study treatment may bear some relationship to the dose level. The potential for
      direct benefit, if any, may also vary with the dose level.

      Subjects will be given one injection of CD30.CAR T cells. The injection will be on Day 0. The
      subject may be given a dose of Benadryl and Tylenol before the injection of T cells to
      minimize any possible allergic reaction. The injection will take 1-10 minutes. The subject
      will be monitored in the clinic after each injection for up to 3 hours.

      At the discretion of the study doctor, if the subject has stable disease (the lymphoma did
      not grow) or there is a reduction in the size of the lymphoma on imaging studies at week 8
      after the T-cell infusion or on subsequent evaluations, then the subject can receive up to
      six additional doses of the T cells at 8 to 12 weeks intervals. After each T cell injection,
      the subject will be monitored as described above.

      If the subject is not post autologous transplant they will receive treatment with
      cyclophosphamide and fludarabine (chemotherapy drugs) before the CD30.CAR T cells. These
      drugs will decrease the numbers of the patient's T cells before the CD30.CAR T cells are
      infused. Although the investigators do not expect any effect on the tumor with the dose that
      the patient will receive, these drugs are part of many regimens that are used to treat
      lymphoma or leukemia.

      To learn more about the way the CD30.CAR T cells are working and how long they last in the
      body, extra blood will be drawn. On the day that the subject receives the cells, blood will
      be taken before the cells are given and several hours afterwards. Other blood will be drawn
      at 1 week, 2 weeks, 3 weeks (optional), 4 weeks, 6 weeks and 8 weeks, every 3 months for 1
      year, every 6 months for 4 years, then yearly for a total of 15 years.
    

Trial Arms

NameTypeDescriptionInterventions
CD30.CAR T CellsExperimentalEach patient will receive one infusion of CAR modified T cells. Unless post autologous transplant, patients will receive Cyclophosphamide and Fludarabine to induce lymphopenia. Patients post autologous stem cell transplantation will receive T cell infusion starting at least 14 days after the date of transplant, unless there is clear evidence of relapse, then T-cell infusion can occur at any time after transplant. No lymphodepleting chemotherapy will be given to these patients.
  • Cyclophosphamide
  • Fludarabine

Eligibility Criteria

        PROCUREMENT Inclusion Criteria:

          1. Diagnosis of relapsed/refractory HL or NHL.

          2. CD30 positive tumor as assayed in a CLIA certified pathology laboratory (result can be
             pending at this time)

          3. Hgb ≥ 7.0 (may be a transfused value)

          4. Informed consent explained to, understood by and signed by patient/guardian.
             Patient/guardian given copy of informed consent.

          5. Karnofsky or Lansky score of > 60%

        TREATMENT Inclusion Criteria:

          1. Diagnosis of relapsed/refractory HL or NHL.

          2. CD30-positive tumor as assayed in a CLIA certified pathology laboratory.

          3. Age 16 to 75 for the first three patients on a dose level; thereafter, if no DLT,
             patients aged 12 to 75 can be treated on that dose level.

          4. Bilirubin 1.5 times or less than the upper limit of normal.

          5. AST 3 times or less than the upper limit of normal.

          6. Estimated GFR > 70 mL/min.

          7. Pulse oximetry of > 90% on room air

          8. EKG shows no significant arrhythmias

          9. Karnofsky or Lansky score of > 60%.

         10. Available autologous T cells with greater than or equal to 15% expression of CD30CAR
             determined by flow-cytometry.

         11. Recovered from all acute non-hematologic toxic effects of all prior chemotherapy.

         12. Adequate pulmonary function with FEV1, FVC and DLCO greater than or equal to 50% of
             expected corrected for hemoglobin.

         13. Sexually active patients must be willing to utilize one of the more effective birth
             control methods during the study and for 6 months after the study is concluded. The
             male partner should use a condom.

         14. Informed consent explained to, understood by and signed by patient or guardian.

        PROCUREMENT Exclusion Criteria:

          1. Active infection with HIV or HTLV (can be pending at this time).

          2. Active bacterial, fungal or viral infection.

        TREATMENT Exclusion Criteria:

          1. Currently receiving any investigational agents or received any tumor vaccines within
             the previous six weeks.

          2. Received anti-CD30 antibody-based therapy within the previous 4 weeks.

          3. Subjects with rapidly progressive disease, defined as kinetic failure to previous
             chemotherapy.

          4. Bulky disease (defined as a 10 cm mass or mediastinal disease with a transverse
             diameter exceeding 33% of the transthoracic diameter).

          5. History of hypersensitivity reactions to murine protein-containing products.

          6. Pregnant or lactating.

          7. Tumor in a location where enlargement could cause airway obstruction.

          8. Current use of systemic corticosteroids at a dose equivalent to 0.5 mg/kg/day of
             prednisone or higher.

          9. Active hemorrhagic cystitis.

         10. Active bacterial, viral or fungal infection.

         11. Symptomatic cardiac disease (NYHA Class III or IV disease).
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Patients with Dose-Limiting Toxicities (DLT)
Time Frame:6 weeks
Safety Issue:
Description:Each treated patient will be followed for 6 weeks post the T-cell infusion for the evaluation of DLTs.

Secondary Outcome Measures

Measure:Median Number of T cells transduced with the vector
Time Frame:15 years
Safety Issue:
Description:The investigators will monitor the persistence of these infused cells by measuring the level of the transgene by both phenotypic and molecular analyses.
Measure:Overall Response Rate
Time Frame:8 weeks
Safety Issue:
Description:Although response is not the primary endpoint of this trial, investigators will summarize tumor response by calculating overall response rates along with exact 95% binomial confidence intervals.
Measure:Mean Number of T cells transduced with the vector
Time Frame:15 years
Safety Issue:
Description:The investigators will monitor the persistence of these infused cells by measuring the level of the transgene by both phenotypic and molecular analyses.

Details

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

Trial Keywords

  • chimeric antigen receptors
  • immunotherapy
  • CAR T-cells
  • lymphoma
  • Cyclophosphamide
  • fludarabine

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