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 the investigators 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. 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.
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
Drug | Synonyms | Arms |
---|
Dose Level 1A: 2 x 10^7 cells/m2 | | Arm A: Treatment with lymphodepletion chemotherapy |
Dose Level 2A: 6 x 10^7 cells/m2 | | Arm A: Treatment with lymphodepletion chemotherapy |
Dose Level 3A: 2 x 10^8 cells/m2 | | Arm A: Treatment with lymphodepletion chemotherapy |
Dose Level 2B | | Arm B: Treatment without lymphodepletion chemotherapy |
Dose Level 3B | | Arm 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 the investigators 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. 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A: Treatment with lymphodepletion chemotherapy | Experimental | C7R-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 chemotherapy | Experimental | C7R-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: | 1. Dose limiting toxicity rate (DLT) by Common Terminology Criteria for Adverse Events v5.0 |
Time Frame: | 28 days post infusion |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | 1. Response rate by Lymphoma Response to Immunomodulatory Therapy (LYRIC) criteria |
Time Frame: | 6 weeks (±2 weeks) post infusion |
Safety Issue: | |
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. |
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
April 1, 2021