Cytotoxic T-Lymphocytes for EBV-positive Lymphoma, GRALE
NCT ID: NCT01555892
Last Updated: 2025-11-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1
136 participants
INTERVENTIONAL
2013-01-14
2027-07-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Some of these patients show signs of virus that is called Epstein Barr virus (EBV) that causes mononucleosis or glandular fever ("mono" or the "kissing disease") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with HD and NHL, suggesting that it may play a role in causing Lymphoma. The cancer cells and some immune system cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if special white blood cells, called GRALE T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor.
We have used this sort of therapy to treat a different type of cancer called post transplant lymphoma. In this type of cancer the tumor cells have 9 proteins made by EBV on their surface. We grew T cells in the lab that recognized all 9 proteins and were able to successfully prevent and treat post transplant lymphoma. However, in HD and NHL, T/NK-lymphoproliferative disease, and CAEBV, the tumor cells and B cells only express 4 EBV proteins. In a previous study, we made T cells that recognized all 9 proteins and gave them to patients with HD. Some patients had a partial response to this therapy but no patients had a complete response. We then did follow up studies where we made T cells that recognized the 2 EBV proteins seen in patients with lymphoma, T/NK-lymphoproliferative disease and CAEBV. We have treated over 50 people on those studies. About 60% of those patients who had disease at the time they got the cells had responses including some patients with complete responses. This study will expand on those results and we will try and make the T cells in the lab in a simpler faster way. These cells are called GRALE T cells. These GRALE T cells are an investigational product not approved by the FDA.
The purpose of this study is to find the largest safe dose of LMP-specific cytotoxic GRALE T cells created using this new manufacturing technique. We will learn what the side effects are and to see whether this therapy might help patients with HD or NHL or EBV associated T/NK-lymphoproliferative disease or CAEBV.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
In this study, patients may also receive cyclophosphamide and fludarabine. These two drugs are standard chemotherapy medicines and may be given before the T cells to make space in the blood for the T cells to grow after receiving them. These drugs will be given intravenously daily over three days.
The GRALE T cells will then be thawed and injected into the subject over 1-10 minutes. Initially, two doses of GRALE T cells will be given 2 weeks apart.
If after the 2nd infusion there is a reduction in the size of the lymphoma on CT or MRI scan as assessed by a radiologist, the subject can receive additional doses of the GRALE T cells if they wish (up to 6 times). Follow up testing will be collected just like after the 1st infusion.
All of the treatments will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.
We will follow the subjects after the injections. They will either be seen in the clinic or the subject will be contacted by a research nurse yearly for 5 years.
If they receive additional doses of the GRALE T cells as described above, they will be followed until 5 years after the last dose of GRALE T-cells.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
EBV-specific T cells: A
Group A: Patients in second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiple relapsed patients in remission who are at a high risk of relapse)\*\* or any patient with primary disease or in first or subsequent remission if immunosuppressive chemotherapy is contraindicated.
Patients may receive cells with or without lymphodepletion.
Patients will be treated at Dose Level 3. Each patient will receive 2 injections, 14 days apart, according to the following dosing schedule:
Day 0: 1 x 10\^8 cells/m2
Day 14: 2 x 10\^8 cells/m2
\*\* Patients with relapsed or refractory lymphoma that are eligible for a stem cell transplant will not be treated on this study as an alternative to transplant.
EBV-specific T cells: A
Patients may receive cells with or without lymphodepletion. Dose Level 3: 1 x 10\^8 cells/m2 + 2 x 10\^8 cells/m2
EBV-specific T cells: B
Group B: Patients in remission or with minimal residual disease (MRD) status after autologous or syngeneic SCT.
Patients may receive cells with or without lymphodepletion.
Patients will be treated at Dose Level 3. Each patient will receive 2 injections, 14 days apart, according to the following dosing schedule:
Day 0: 1 x 10\^8 cells/m2
Day 14: 2 x 10\^8 cells/m2
EBV-specific T cells: B
Patients may receive cells with or without lymphodepletion. Dose Level 3: 1 x 10\^8 cells/m2 + 2 x 10\^8 cells/m2
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
EBV-specific T cells: A
Patients may receive cells with or without lymphodepletion. Dose Level 3: 1 x 10\^8 cells/m2 + 2 x 10\^8 cells/m2
EBV-specific T cells: B
Patients may receive cells with or without lymphodepletion. Dose Level 3: 1 x 10\^8 cells/m2 + 2 x 10\^8 cells/m2
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. EBV positive tumor (can be pending at this time)
3. Weighs at least 12kg
4. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
1. Any patient, regardless of age or sex, with EBV-positive Hodgkin's or non-Hodgkin's Lymphoma (regardless of histologic subtype), or EBV (associated)-T/NK-lymphoproliferative disease or Severe Chronic Active EBV (CAEBV)\* and
In second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiply relapsed patients in remission who have a high risk of relapse)\*\* OR any patient with primary disease or in first remission if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a Richter's transformation of CLL. (Group A)
OR
In remission or with minimal residual disease status after autologous or syngeneic SCT. (Group B)
2. EBV positive tumor
3. Patients with bilirubin less than or equal to 3x upper limit of normal, AST less than or equal 5x upper limit of normal, and hemoglobin greater than or equal to 7.0 (may be a transfused value).
4. Patients with a creatinine less than or equal to 2x upper limit of normal for age
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. PD1/PDL inhibitors will be allowed if medically indicated.
7. Patients with a Karnofsky/Lansky score of greater than or equal to 50
8. 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.
9. Informed consent explained to, understood and signed by patient/guardian. Patient/guardian given copy of informed consent.
* CAEBV is defined as patients with high EBV viral load in plasma or PBMC (\> 4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV
* Patients with relapsed or refractory lymphoma that are eligible for a stem cell transplant will not be treated on this study as an alternative to transplant.
Exclusion Criteria
1. Pregnant or lactating
2. Severe intercurrent infection.
3. Current use of systemic corticosteroids \> 0.5 mg/kg/day
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
The Methodist Hospital Research Institute
OTHER
Center for Cell and Gene Therapy, Baylor College of Medicine
OTHER
National Institutes of Health (NIH)
NIH
National Cancer Institute (NCI)
NIH
Harris County Hospital District
OTHER_GOV
Baylor College of Medicine
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Helen Heslop
Professor
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Helen E Heslop, MD
Role: PRINCIPAL_INVESTIGATOR
Baylor College of Medicine
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Harris Health System (includes ben Taub General Hospital and Smith)
Houston, Texas, United States
Houston Methodist Hospital
Houston, Texas, United States
Texas Children's Hospital
Houston, Texas, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Martha Mims, MD
Role: primary
Helen E Heslop, MD
Role: primary
Vicky Torrano
Role: backup
Helen E Heslop, MD
Role: primary
Vicky Torrano
Role: backup
References
Explore related publications, articles, or registry entries linked to this study.
Sarathkumara YD, Van Bibber NW, Liu Z, Heslop HE, Rouce RH, Coghill AE, Rooney CM, Proietti C, Doolan DL. Differential antibody response to EBV proteome following EBVST immunotherapy in EBV-associated lymphomas. Blood Adv. 2025 Apr 8;9(7):1658-1669. doi: 10.1182/bloodadvances.2024014937.
Sharma S, Mehta NU, Sauer T, Rollins LA, Dittmer DP, Rooney CM. Cotargeting EBV lytic as well as latent cycle antigens increases T-cell potency against lymphoma. Blood Adv. 2024 Jul 9;8(13):3360-3371. doi: 10.1182/bloodadvances.2023012183.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
GRALE
Identifier Type: OTHER
Identifier Source: secondary_id
H-29617-GRALE
Identifier Type: -
Identifier Source: org_study_id