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EBV Specific T-Lymphocytes for Treatment of EBV-Positive Lymphoma (CILESTE)

Primary Purpose

EBV-Related Hodgkin Lymphoma, Lymphoproliferative Disorders, EBV Related Non-Hodgkin's Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dose Level 1A: 2 x 10^7 cells/m2
Dose Level 2A: 6 x 10^7 cells/m2
Dose Level 2B: 6 x 10^7 cells/m2
Dose Level 3B: 2 x 10^8 cells/m2
Dose Level 3A: 2 x 10^8 cells/m2
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for EBV-Related Hodgkin Lymphoma focused on measuring non-Hodgkin's Lymphoma, EBV (associated)-T/NK-lymphoproliferative disease, EBV SPECIFIC T-LYMPHOCYTES, EBV, Hodgkin's Lymphoma, lymphoma relapse

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers
  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 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

    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.

    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.

Sites / Locations

  • Houston Methodist HospitalRecruiting
  • Texas Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A: Treatment without lymphodepletion chemotherapy

Arm B: Treatment with lymphodepletion chemotherapy

Arm Description

C7R-EBVSTs Group B will be activated if only limited expansion and clinical efficacy is observed in Group A

C7R-EBVSTs with lymphodepletion chemotherapy

Outcomes

Primary Outcome Measures

1. Dose limiting toxicity rate (DLT) by Common Terminology Criteria for Adverse Events v5.0
Dose-limiting toxicity is defined as 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

1. Response rate by Lymphoma Response to Immunomodulatory Therapy (LYRIC) criteria
The response rate is calculated as the percentage of patients whose best response is either complete response or partial response according to Lyric criteria.

Full Information

First Posted
December 7, 2020
Last Updated
March 22, 2023
Sponsor
Baylor College of Medicine
Collaborators
The Methodist Hospital Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT04664179
Brief Title
EBV Specific T-Lymphocytes for Treatment of EBV-Positive Lymphoma
Acronym
CILESTE
Official Title
Constitutive IL7 (C7R) Modified EBV Specific T-Lymphocytes for Treatment of EBV-Positive Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 31, 2022 (Actual)
Primary Completion Date
March 30, 2024 (Anticipated)
Study Completion Date
March 30, 2039 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine
Collaborators
The Methodist Hospital Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is for patients that have a type of lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease which has come back or has not gone away after treatment, including the best treatment the investigators know for these diseases. Some patients with Lymphoma or T/NK-lymphoproliferative disease 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 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. The investigators 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. The investigators 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 the investigators will add a new gene to the EBV T cells that can cause the cells to live longer called C7R. The investigators know that T cells need substances called cytokines to survive and the cells may not get enough cytokines after infusion into the body. The investigators 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, the investigators 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. The investigators 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 should plan to stay in Houston for up to 2 weeks after the infusion so the investigators can monitor them for side effects. Patients will have follow-up visits with the clinic (at scheduled visits weeks 2 and 6, and nursing follow-up at weeks 1, 2, 4, and 6; months 3, 6, 9, and 12; and annually for the next 15 years). Patients will have scheduled disease evaluations after the T-cell injection (at week 6 +/- 2 weeks 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 the investigators 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 the investigators 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. The investigators 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, the investigators 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
EBV-Related Hodgkin Lymphoma, Lymphoproliferative Disorders, EBV Related Non-Hodgkin's Lymphoma
Keywords
non-Hodgkin's Lymphoma, EBV (associated)-T/NK-lymphoproliferative disease, EBV SPECIFIC T-LYMPHOCYTES, EBV, Hodgkin's Lymphoma, lymphoma relapse

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Treatment without lymphodepletion chemotherapy
Arm Type
Experimental
Arm Description
C7R-EBVSTs Group B will be activated if only limited expansion and clinical efficacy is observed in Group A
Arm Title
Arm B: Treatment with lymphodepletion chemotherapy
Arm Type
Experimental
Arm Description
C7R-EBVSTs with lymphodepletion chemotherapy
Intervention Type
Biological
Intervention Name(s)
Dose Level 1A: 2 x 10^7 cells/m2
Intervention Description
2 x 10^7 cells/m2
Intervention Type
Biological
Intervention Name(s)
Dose Level 2A: 6 x 10^7 cells/m2
Intervention Description
6 x 10^7 cells/m2
Intervention Type
Biological
Intervention Name(s)
Dose Level 2B: 6 x 10^7 cells/m2
Intervention Description
6 x 10^7 cells/m2
Intervention Type
Biological
Intervention Name(s)
Dose Level 3B: 2 x 10^8 cells/m2
Intervention Description
2 x 10^8 cells/m2
Intervention Type
Biological
Intervention Name(s)
Dose Level 3A: 2 x 10^8 cells/m2
Intervention Description
2 x 10^8 cells/m2
Primary Outcome Measure Information:
Title
1. Dose limiting toxicity rate (DLT) by Common Terminology Criteria for Adverse Events v5.0
Description
Dose-limiting toxicity is defined as 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.
Time Frame
28 days post infusion
Secondary Outcome Measure Information:
Title
1. Response rate by Lymphoma Response to Immunomodulatory Therapy (LYRIC) criteria
Description
The response rate is calculated as the percentage of patients whose best response is either complete response or partial response according to Lyric criteria.
Time Frame
6 weeks (±2 weeks) post infusion

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA AT TIME OF PROCUREMENT 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 who may subsequently be eligible for the treatment component EBV positive tumor (can be pending) Weighs at least 10 kg Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given a copy of informed consent. INCLUSION CRITERIA AT TIME OF INFUSION 1) Any patient regardless of age or sex, with diagnosis of either EBV positive Hodgkin's lymphoma EBV positive non-Hodgkin's Lymphoma (regardless of histologic subtype) EBV (associated)-T/NK-lymphoproliferative disease 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. 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. EXCLUSION CRITERIA AT TIME OF PROCUREMENT 1. Known pregnancy or actively breastfeeding (pregnancy test is not required at the time of procurement). EXCLUSION CRITERIA AT TIME OF INFUSION Pregnant or breastfeeding Active and uncontrolled bacterial, viral or fungal infection Current use of systemic corticosteroids (prednisone equivalent >0.5 mg/kg/day) Bulky disease resulting in airway obstruction or risk for airway obstruction with further enlargement.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bilal Omer, MD
Phone
832-824-6855
Email
bomer@bcm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bilal Omer, MD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Houston Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bilal Omer, MD
Phone
832-824-6855
Email
bomer@bcm.edu
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bilal Omer, MD
Phone
832-824-6855
Email
bomer@bcm.edu

12. IPD Sharing Statement

Learn more about this trial

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

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