Clinical Trials /

Allogeneic CD30.CAR-EBVSTs in Patients With Relapsed or Refractory CD30-Positive Lymphomas

NCT04288726

Description:

This study involved patients that have a cancer called diffuse large B cell lymphoma (DLBCL), NK and T cell lymphomas (NK/TL), classical Hodgkin lymphoma (cHL) or post-transplantation lymphoproliferative disease (PTLD) (hereafter these 4 diseases will be referred to as lymphoma). Patients lymphoma has come back or not gone away after treatment. Because there is no standard treatment for the patients cancer at this time or because the currently used treatments do not work fully in all cases, the patients are being asked to volunteer in this research study. In this study the investigators want to test a type of T cell made from a normal donor. The T cells the investigators will use are called Epstein Barr virus (EBV) specific T cells (EBVSTs) and are cells that the investigators have trained in the laboratory to recognize a EBV which is the virus that causes mono or kissing disease. Some patients with lymphoma have EBV in their cancer cells. Researchers have given T cell lines from normal donor EBVSTs to lymphoma patients who have EBV in their lymphoma cells and have seen responses in about half the patients. The cells have have been generated and are frozen in a bank. The cells are called "allogeneic" (meaning the donor is not related to the patient). CD30.CAR in EBV-specific T cells (called allogeneic CD30.CAR-EBVST) from the blood of healthy donors. The investigators are giving the cells to patients with lymphoma cells that express CD30. If the lymphoma cells also express EBV there may be some benefit from targeting both proteins. The purpose of this study is to find out the highest safe dose of allogeneic CD30.CAR-EBVST cells given following chemotherapy and used to treat lymphoma. The investigators will learn the side effects of CD30.CAR-EBVST cells in patients and see whether this therapy may help lymphoma patients

Related Conditions:
  • Aggressive Non-Hodgkin Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Hodgkin Lymphoma
  • Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
  • Peripheral T-Cell Lymphoma
  • Post-Transplant Lymphoproliferative Disorder
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Allogeneic CD30.CAR-EBVSTs in Patients With Relapsed or Refractory CD30-Positive Lymphomas
  • Official Title: A Phase 1 Study Evaluating the Safety and Activity of Allogeneic CD30 Chimeric Antigen Receptor Epstein-Barr Virus-Specific T Lymphocytes (CD30.CAR-EBVSTs) in Patients With Relapsed or Refractory CD30-Positive Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: H-46862 BESTA
  • NCT ID: NCT04288726

Conditions

  • Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type
  • Classical Hodgkin Lymphoma
  • Post-transplant Lymphoproliferative Disorder

Interventions

DrugSynonymsArms
CD30.CAR-EBVST cellsAllogeneic CD30 Chimeric Antigen Receptor Epstein-Barr Virus-Specific T LymphocytesTreatment Phase

Purpose

This study involved patients that have a cancer called diffuse large B cell lymphoma (DLBCL), NK and T cell lymphomas (NK/TL), classical Hodgkin lymphoma (cHL) or post-transplantation lymphoproliferative disease (PTLD) (hereafter these 4 diseases will be referred to as lymphoma). Patients lymphoma has come back or not gone away after treatment. Because there is no standard treatment for the patients cancer at this time or because the currently used treatments do not work fully in all cases, the patients are being asked to volunteer in this research study. In this study the investigators want to test a type of T cell made from a normal donor. The T cells the investigators will use are called Epstein Barr virus (EBV) specific T cells (EBVSTs) and are cells that the investigators have trained in the laboratory to recognize a EBV which is the virus that causes mono or kissing disease. Some patients with lymphoma have EBV in their cancer cells. Researchers have given T cell lines from normal donor EBVSTs to lymphoma patients who have EBV in their lymphoma cells and have seen responses in about half the patients. The cells have have been generated and are frozen in a bank. The cells are called "allogeneic" (meaning the donor is not related to the patient). CD30.CAR in EBV-specific T cells (called allogeneic CD30.CAR-EBVST) from the blood of healthy donors. The investigators are giving the cells to patients with lymphoma cells that express CD30. If the lymphoma cells also express EBV there may be some benefit from targeting both proteins. The purpose of this study is to find out the highest safe dose of allogeneic CD30.CAR-EBVST cells given following chemotherapy and used to treat lymphoma. The investigators will learn the side effects of CD30.CAR-EBVST cells in patients and see whether this therapy may help lymphoma patients

Detailed Description

      Earlier, healthy donors gave blood for us to make CD30.CAR-EBVST cells in the laboratory.
      These cells were grown and frozen and the investigators will select the donor which the
      investigators think is the best match for the patient. 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 CD30.CAR-EBVST cells. Once the lower 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
      infusion will be stopped. Both the risks and benefits of this study may be dose related. The
      investigators don't know the best dose that will provide benefit while minimizing the risks.

      To enroll on this study, patients will need to have recovered from toxic effects of previous
      chemotherapy and not be receiving any other investigational agents. Patients cannot have
      received any tumor vaccines within the previous six weeks.

      If patients agree to take part in this study, the investigators will ask the patients to
      adhere to the following study visits and procedure. After patients have signed the consent
      form, patients are required to come to the hospital for a series of standard medical
      screening tests, lymphodepletion chemotherapy with cyclophosphamide and fludarabine, infusion
      with CD30.CAR-EBVST cell treatment and follow-up visits (See details below).

        1. Screening tests

           Screening tests include:

             -  Blood tests [Human Leukocyte Antigen (HLA) testing] to help us identify the best
                match for patients from the banked CD30.CAR-EBVST cells.

             -  Blood tests for viruses such as human immunodeficiency virus [HIV], human T cell
                lymphotropic virus [HTLV], hepatitis B virus and hepatitis C virus.

             -  Tumor biopsy test to check the status of CD30.

           Once the investigators find that patients are eligible for this study, patients will be
           called for additional screening tests before treatment day. The screening tests include:

             -  Physical examination

             -  Vital signs tests to measure temperature, pulse, respiratory rate and blood
                pressure

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

             -  Urine test

             -  Pregnancy test for women of child-bearing potential

             -  Measurements of tumor by routine imaging studies

        2. Lymphodepletion chemotherapy 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 the blood stream. Because of that, if
           patients have NOT had a bone marrow or stem cell transplant recently, patients will
           receive treatment with cyclophosphamide and fludarabine (chemotherapy drugs) before
           patients receive the CD30.CAR-EBVST cells if patients doctor thinks this is appropriate.
           This is called "lymphodepletion". These drugs will decrease the numbers of patients own
           T cells before the investigators inject the CD30.CAR-EBVST cells. Although the
           investigators do not expect any effect on the patients tumor with the dose that the
           patients will receive, these drugs are part of many regimens that are used to treat
           lymphoma.

        3. Treatment with CD30.CAR-EBVST cells Patients will be given one injection of
           CD30.CAR-EBVST cells. The CD30.CAR-EBVST cells will be injected into the vein through an
           IV line at the assigned dose. Before patients receive the injection, patients may be
           given a dose of acetaminophen or anti-histamine (Benadryl for example) to minimize any
           possible allergic reaction. The injection of CD30.CAR-EBVST cells will take within 10
           minutes. The investigators will follow patients in the clinic after each injection for
           up to 3 hours.

           At the discretion of the study doctor, if patients have stable disease (the lymphoma did
           not grow) or there is a reduction in the size of the patients lymphoma on imaging
           studies at week 6 after T-cell infusion or on subsequent evaluations, then patients may
           receive up to two additional doses of the CD30.CAR-EBVST cells at approximately 6 weeks
           intervals if patients wish to. Lymphodepletion chemotherapy may also be administered
           before additional doses of CD30.CAR-EBVST infusion. After each T-cell infusion, patients
           will be monitored to ensure that participants don't have a reaction to the infusion.

        4. Follow-up visits

      On follow-up visits after treatment, patients will also receive a series of standard medical
      tests:

        -  Physical examination

        -  Vital sign tests to measure temperature, pulse, respiratory rate and blood pressure

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

        -  Urine tests (if clinically necessary)

        -  Pregnancy test for women of child-bearing potential (if clinically necessary)

        -  Measurements of tumor by routine imaging studies

      After infusion of CD30.CAR-EBVST cells,the patients blood will be collected on follow-up
      visits at week 1, week 2, week 3, week 4, week 6, week 8, every 3 months for 1 year, every 6
      months for 4 more years. Blood samples and tumor biopsies will also be periodically
      collected, based on the patients doctor's discretion for exploratory tests in the laboratory.
      After 5 years , in the event there is suspected or new cancer is detected, additional blood
      sample will also be collected for additional tests.

      To learn more about the way the CD30.CAR-EBVST cells are working and how long they last in
      the body, the investigators will draw blood. The total amount of blood collected on any day
      is about 4-18 teaspoons (18-87 ml). This volume is considered safe but may be decreased if
      the patients are anemic. Patients blood will be drawn from a central line if participants
      have one. The total blood drawn during the patients participation in this study will not
      exceed 110 teaspoons (546 ml).

      The investigators will also look at any scans or biopsies patients have had as standard of
      care.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment PhaseExperimentalThree dose levels will be evaluated based on safety data from our current study of CD30 CAR T cells. Cohorts of three to six patients will be enrolled at each dose level The dose is based on the number of CD.30 CAR-EBVT-expressing cells administered. The total number of dose levels evaluated will depend upon toxicities experienced. Dose level cohorts will be numbered sequentially. Dose Level 1: 4 × 107 CD30.CAR-EBVST cells Dose Level 2: 1 × 108 CD30.CAR-EBVST cells Dose Level 3: 4 × 108 CD30.CAR-EBVST cells
  • CD30.CAR-EBVST cells

Eligibility Criteria

        Inclusion Criteria:

          1. Diagnosis and clinical course falling into one of the following categories:

               1. Hodgkin lymphoma

               2. Aggressive non-Hodgkin lymphoma

               3. ALK-negative anaplastic T cell lymphoma or other peripheral T-cell lymphoma

               4. ALK-positive anaplastic T cell lymphoma

          2. CD30-positive tumor as assayed in a CLIA certified Pathology Laboratory.

          3. Age 12 to 75.

          4. Bilirubin 2 times (or 3 times if the patient has Gilbert syndrome) 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 ≥15% expression of CD30CAR determined by
             flow-cytometry.

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

         12. 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. Patient
        or guardian given a copy of the informed consent form.

        Exclusion Criteria:

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

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

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

          4. Pregnant or lactating.

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

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

          7. Active hemorrhagic cystitis.

          8. Active significant, uncontrolled bacterial, viral or fungal infection.

          9. 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:Dose limiting toxicity rate (DLT) by CTCAE 5.0
Time Frame:28 days
Safety Issue:
Description:Any Grade 5 event, / Non-hematologic dose-limiting toxicity is any Grade 3 or Grade 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours, / Grade 2-4 allergic reaction to T-Cells, / Grade 3-4 GVHD, / Grade 3-4 CRS. Toxicity will be evaluated according to the CTCAE Version 5.0. GVHD will be graded by the method of Przepiorka et al.

Secondary Outcome Measures

Measure:Rate of Anti-Tumor effect Objective Response (OR)
Time Frame:6 to 8 weeks post CTL infusion
Safety Issue:
Description:Objective response rate is defined as complete response and partial response
Measure:Duration of response
Time Frame:Up to 5 years
Safety Issue:
Description:Response duration will be measured from the time of initial response until documented tumor progression.
Measure:Stable disease (SD) rate
Time Frame:6 to 8 weeks post CTL infusion
Safety Issue:
Description:SD will be defined as the proportion of patients that have stable disease
Measure:Duration of SD
Time Frame:Up to 5 years
Safety Issue:
Description:Stable disease is measured from the start of the treatment until the criteria for progression are met.
Measure:Progression free survival (PFS)
Time Frame:Up to 5 years
Safety Issue:
Description:PFS is defined as the time from treatment until objective tumor progression or death, whichever occurs first.

Details

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

Trial Keywords

  • CD30-Positive Lymphoma
  • Hodgkin lymphoma
  • non-Hodgkin lymphoma
  • CD30 CAR

Last Updated

February 27, 2020