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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04288726
Recruitment Status : Recruiting
First Posted : February 28, 2020
Last Update Posted : March 9, 2023
The Methodist Hospital Research Institute
Information provided by (Responsible Party):
Carlos Ramos, Baylor College of Medicine

Brief Summary:

This study involved patients that have a cancer called diffuse large B cell lymphoma (DLBCL), NK and T cell lymphomas (NK/TL) or classical Hodgkin lymphoma (cHL) (hereafter these 3 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

Condition or disease Intervention/treatment Phase
Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type Classical Hodgkin Lymphoma Biological: CD30.CAR-EBVST cells Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 16, 2020
Estimated Primary Completion Date : June 1, 2025
Estimated Study Completion Date : June 1, 2037

Arm Intervention/treatment
Experimental: Treatment Phase

Three 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
Biological: CD30.CAR-EBVST cells

The dose is based on the number of CD30.CAR-expressing cells. In our previous study the highest dose was 2 × 108 cells/m2 and we did not reach an MTD. We will be splitting the total dose between 2 infusions three days apart to improve tumor exposure to CAR-T cells.

There will be a gap of 4 weeks between the first and second patient on each dose level.

On Days 0 and 3 ±1 of study, patients will receive half their planned dose of investigational T cell product by IV infusion over approximately 1 to 10 minutes in an expected volume of 1 to 50 mL.

Other Name: Allogeneic CD30 Chimeric Antigen Receptor Epstein-Barr Virus-Specific T Lymphocytes

Primary Outcome Measures :
  1. Dose limiting toxicity rate (DLT) by CTCAE 5.0 [ Time Frame: 28 days ]
    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 :
  1. Rate of Anti-Tumor effect Objective Response (OR) [ Time Frame: 6 to 8 weeks post CTL infusion ]
    Objective response rate is defined as complete response and partial response

  2. Duration of response [ Time Frame: Up to 5 years ]
    Response duration will be measured from the time of initial response until documented tumor progression.

  3. Stable disease (SD) rate [ Time Frame: 6 to 8 weeks post CTL infusion ]
    SD will be defined as the proportion of patients that have stable disease

  4. Duration of SD [ Time Frame: Up to 5 years ]
    Stable disease is measured from the start of the treatment until the criteria for progression are met.

  5. Progression free survival (PFS) [ Time Frame: Up to 5 years ]
    PFS is defined as the time from treatment until objective tumor progression or death, whichever occurs first.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   12 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 allogeneic 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.
  13. 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. Received an investigational cell therapy or vaccine within the past 6 weeks.
  2. Received an investigational small molecule drug within the past 2 weeks.
  3. Received CD30 antibody-based therapy within the previous 4 weeks.
  4. Received gemcitabine-containing chemotherapy within the previous 12 weeks
  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 (determined at the investigators' discretion).
  8. Current use of systemic corticosteroids at a dose equivalent to higher than 10 mg/day of prednisone.
  9. Active significant, uncontrolled bacterial, viral or fungal infection.
  10. Symptomatic cardiac disease (NYHA Class III or IV disease).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04288726

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Contact: Carlos Ramos, MD 832-824-4817
Contact: Vicky Torrano (832) 824-7821

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United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Carlos Ramos, MD    713-441-1450   
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Carlos Ramos, MD    713-441-1450   
Sponsors and Collaborators
Baylor College of Medicine
The Methodist Hospital Research Institute
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Principal Investigator: Carlos Ramos, MD Baylor College of Medicine
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Responsible Party: Carlos Ramos, Associate Professor, Baylor College of Medicine Identifier: NCT04288726    
Other Study ID Numbers: H-46862 BESTA
First Posted: February 28, 2020    Key Record Dates
Last Update Posted: March 9, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Carlos Ramos, Baylor College of Medicine:
CD30-Positive Lymphoma
Hodgkin lymphoma
non-Hodgkin lymphoma
Additional relevant MeSH terms:
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Hodgkin Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases