Clinical Trials /

EBV Specific T-Lymphocytes for Treatment of EBV-Positive Lymphoma

NCT04664179

Description:

This study is for patients that have a type of lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease or severe chronic active Epstein Barr Virus (CAEBV) which has come back or has not gone away after treatment, including the best treatment we know for these diseases. Some patients with Lymphoma or T/NK-lymphoproliferative disease or CAEBV show signs of virus that is sometimes called Epstein Barr virus (EBV) that causes mononucleosis or glandular fever ("mono") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with Hodgkin's and non-Hodgkin Lymphoma, suggesting that plays a role in causing Lymphoma. The cancer cells (in lymphoma) and some immune system cells (in CAEBV) infected by EBV are able to hide from the body's immune system and escape destruction. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. T cells have been used to treat patients with cancers. T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor. We have treated over 80 people on studies using T cells to target these diseases. About half of those patients who had disease at the time they got the cells had responses including some patients with complete responses. We think that if T cells are able to last longer in the body, they may have a better chance of killing EBV and EBV infected tumor cells. Therefore, in this study we will add a new gene to the EBV T cells that can cause the cells to live longer called C7R. We know that T cells need substances called cytokines to survive and the cells may not get enough cytokines after infusion into the body. We have added the gene C7R that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time. The purpose of this study is to find the largest safe dose of C7R-EBV T cells, and additionally to evaluate how long they can be detected in the blood and what affect they have on cancer.

Related Conditions:
  • Lymphoma
  • Lymphoproliferative Disorder
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: EBV Specific T-Lymphocytes for Treatment of EBV-Positive Lymphoma
  • Official Title: Constitutive IL7 (C7R) Modified EBV Specific T-Lymphocytes for Treatment of EBV-Positive Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: H-47906 CILESTE
  • NCT ID: NCT04664179

Conditions

  • EBV-Related Hodgkin Lymphoma
  • Lymphoproliferative Disorders
  • Chronic EBV (Epstein-Barr Virus) Infection Syndrome
  • EBV Related Non-Hodgkin's Lymphoma

Interventions

DrugSynonymsArms
Dose Level 1A: 2 x 10^7 cells/m2Arm A: Treatment with lymphodepletion chemotherapy
Dose Level 2A: 6 x 10^7 cells/m2Arm A: Treatment with lymphodepletion chemotherapy
Dose Level 3A: 2 x 10^8 cells/m2Arm A: Treatment with lymphodepletion chemotherapy
Dose Level 2BArm B: Treatment without lymphodepletion chemotherapy
Dose Level 3BArm B: Treatment without lymphodepletion chemotherapy

Purpose

This study is for patients that have a type of lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease or severe chronic active Epstein Barr Virus (CAEBV) which has come back or has not gone away after treatment, including the best treatment we know for these diseases. Some patients with Lymphoma or T/NK-lymphoproliferative disease or CAEBV show signs of virus that is sometimes called Epstein Barr virus (EBV) that causes mononucleosis or glandular fever ("mono") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with Hodgkin's and non-Hodgkin Lymphoma, suggesting that plays a role in causing Lymphoma. The cancer cells (in lymphoma) and some immune system cells (in CAEBV) infected by EBV are able to hide from the body's immune system and escape destruction. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. T cells have been used to treat patients with cancers. T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor. We have treated over 80 people on studies using T cells to target these diseases. About half of those patients who had disease at the time they got the cells had responses including some patients with complete responses. We think that if T cells are able to last longer in the body, they may have a better chance of killing EBV and EBV infected tumor cells. Therefore, in this study we will add a new gene to the EBV T cells that can cause the cells to live longer called C7R. We know that T cells need substances called cytokines to survive and the cells may not get enough cytokines after infusion into the body. We have added the gene C7R that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time. The purpose of this study is to find the largest safe dose of C7R-EBV T cells, and additionally to evaluate how long they can be detected in the blood and what affect they have on cancer.

Detailed Description

      The patient will donate blood in order to make C7R-EBV T cells. Depending on how long ago the
      cells were generated, they have been frozen. To get the C7R to be made by the T-cell, we
      inserted a gene into the T-cell. This is done using certain parts of a virus (known as a
      retrovirus) that can carry the gene into the T cells. Because patients receive cells with a
      new gene in them, they will befollowed for a total of 15 years to see if there are any long
      term side effects of gene transfer.

      When they are enrolled in this study, patients are assigned a dose of C7R EBV T cells. The
      assigned dose of cells is based on body weight and height. Patients will receive the C7R EBV
      T cells and may also receive cyclophosphamide and fludarabine (these are standard
      chemotherapy medicines). The chemotherapy medicines may be given before the T cells to make
      space in the blood for the T cells to grow after receiving them.

      If a patient receives chemotherapy medicines, these drugs will be given through an i.v.
      needle inserted in the patient's vein or central line) for 2 days and then fludarabine alone
      on the third day. The patient will be given an injection of C7R EBV T cells into the vein
      through an IV line at the assigned dose.

      Patients may receive Benadryl and Tylenol. The infusion will take between 1 and 10 minutes.
      We will then monitor the patient in the clinic or hospital for about 2 hours. The treatment
      will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston
      Methodist Hospital. Patients may need to stay in Houston for up to 2 weeks after the infusion
      so we can monitor them for side effects.

      Patients will have follow-up visits (at weeks 1, 2, 4, and 6; months 3, 6, 9, and 12; and
      yearly for the next 15 years). Patients will have scheduled disease evaluations after the
      T-cell injection (at week 6 and then as clinically needed). After the disease re-evaluation,
      if the patient's disease has not gotten worse, or if in the future it seems he/she might
      benefit, they may be eligible to receive one additional dose of the T cells. The dose will be
      at the same dose level as the patient's first infusion and separated by at least 6 weeks such
      that we can make sure that the patient has no severe side effects between infusions. If the
      patient receives an additional dose of C7R EBV T-cells, they will need to stay in Houston for
      up to 2 weeks after the infusion as well so we can monitor them for side effects.

      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

        -  Measurements of the tumor by routine imaging studies. We will use the imaging studies
           that have been used in the past to best assess the patient's tumor (Computer Tomogram
           (CT) or Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET/CT)
           and/or Bone Scan).

      Medical tests during and after treatment--

      The patient will receive standard medical tests when they are getting the infusions and
      afterwards:

        -  Physical exams

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

        -  Measurements of the tumor by routine imaging studies approximately 6 weeks after the
           infusion.

      To learn more about the way the C7R EBV T cells are working and how long they last in the
      body, an extra amount of blood will be obtained on the day that chemotherapy starts, the day
      of the T-cell infusion(s) and at the end of the T-cell infusion(s), 1, 2, 4, 6 weeks after
      the T-cell infusion(s) and every 3 months for the 1st year, and annually for the next 15
      years and possibly at additional time points. The amount of blood taken will be based on the
      patient's weight with up to a maximum of 60 mL (12 teaspoons) of blood to be obtained at any
      one time. For children, the total amount of blood drawn will not be more than 3 mL (less than
      1 teaspoon) per 1 kg (2 lbs) of body weight on any one day. This volume is considered safe,
      but may be decreased if the patient is anemic (have a low red blood cell count).

      If the patient has a procedure where tumor samples are obtained, like a repeat bone marrow
      evaluation or tumor biopsy, we will request a sample to be used for research purposes.
      Patients will receive supportive care for any acute or chronic toxicities, including blood
      components or antibiotics, and other intervention as appropriate.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: Treatment with lymphodepletion chemotherapyExperimentalC7R-EBVSTs with lymphodepletion chemotherapy
  • Dose Level 1A: 2 x 10^7 cells/m2
  • Dose Level 2A: 6 x 10^7 cells/m2
  • Dose Level 3A: 2 x 10^8 cells/m2
Arm B: Treatment without lymphodepletion chemotherapyExperimentalC7R-EBVSTs
  • Dose Level 2B
  • Dose Level 3B

Eligibility Criteria

        1. INCLUSION CRITERIA AT TIME OF PROCUREMENT

               1. Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non
                  Hodgkin's Lymphoma, (regardless of the histological subtype) or EBV (associated)-
                  T/NK-lymphoproliferative disease or Severe Chronic Active EBV (CAEBV)* who may
                  subsequently be eligible for the treatment component

               2. EBV positive tumor (can be pending)

               3. Weighs at least 10 kg

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

          2. INCLUSION CRITERIA AT TIME OF INFUSION

             1) Any patient regardless of age or sex, with diagnosis of either

               1. EBV positive Hodgkin's lymphoma

               2. EBV positive non-Hodgkin's Lymphoma (regardless of histologic subtype)

               3. EBV (associated)-T/NK-lymphoproliferative disease

               4. Severe Chronic Active EBV (CAEBV)*

             AND either

             A) In first or subsequent relapse or with persistent active disease despite therapy;
             OR

             B) With active disease if immunosuppressive chemotherapy is contraindicated as
             determined by the study PI, in consultation with the primary provider as needed, e.g.
             patients who develop Hodgkin's disease after solid organ transplantation or if the
             lymphoma is a second malignancy, e.g. a Richter's transformation of CLL.

             *CAEBV is defined as patients with high EBV viral load in plasma or PBMC (>4000
             genomes per microgram PBMC DNA) and/or biopsy tissue positive for EBV

             2) EBV positive tumor confirmed by pathology

             3) Patients with life expectancy ≥ 6 weeks

             4) Patients with bilirubin ≤ 3x upper limit of normal, AST ≤ 5x upper limit of normal,
             creatinine ≤ 2x upper limit of normal for age and Hgb ≥ 7.0 (may be a transfused
             value)

             5) Pulse oximetry of >90% on room air

             6) Patients should have been off other investigational therapy for 4 weeks prior to
             entry in this study.

             7) Patients with a Karnofsky/Lansky score of ≥ 50

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

          3. EXCLUSION CRITERIA AT TIME OF PROCUREMENT

             1. Known pregnancy or actively breastfeeding (pregnancy test is not required at the
             time of procurement).

          4. EXCLUSION CRITERIA AT TIME OF INFUSION

               1. Pregnant or breastfeeding

               2. Active and uncontrolled bacterial, viral or fungal infection

               3. Current use of systemic corticosteroids (prednisone equivalent >0.5 mg/kg/day)

               4. Bulky disease resulting in airway obstruction or risk for airway obstruction with
                  further enlargement.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicity rate (DLT) by CTCAE 5.0
Time Frame:28 days post infusion
Safety Issue:
Description:Any irreversible, life threatening or non-hematologic Grade 3-5 event considered to be primarily related to the EBVST infusion, with the exception of Grade 3-4 expected reactions such as fever and hypotension/ Grade 3-4 CRS toxicity persistent beyond 72 hours

Secondary Outcome Measures

Measure:Response rate by LYRIC criteria
Time Frame:42-56 days post infusion
Safety Issue:
Description:The response rate is defined as the percentage of patients whose best response is either complete response or partial response according to Lyric criteria.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Baylor College of Medicine

Trial Keywords

  • non-Hodgkin's Lymphoma
  • EBV (associated)-T/NK-lymphoproliferative disease
  • Severe Chronic Active EBV (CAEBV)
  • EBV SPECIFIC T-LYMPHOCYTES
  • EBV
  • Hodgkin's Lymphoma
  • lymphoma relapse

Last Updated

December 11, 2020