Cytotoxic T-Lymphocytes for EBV-positive Lymphoma, GRALE
GRALE
Administration of Rapidly Generated EBV-Specific Cytotoxic T-Lymphocytes To Patients With EBV-Positive Lymphoma
3 other identifiers
interventional
136
1 country
3
Brief Summary
Subjects 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, is at risk of coming back, or has not gone away after treatment, including the best treatment investigators know for these diseases. 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. Investigators 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. Investigators 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. Investigators 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, the investigators 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. The investigators then did follow up studies where investigators made T cells that recognized the 2 EBV proteins seen in patients with lymphoma, T/NK-lymphoproliferative disease and CAEBV. Investigators 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 the investigators 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. Investigators 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2013
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 13, 2012
CompletedFirst Posted
Study publicly available on registry
March 16, 2012
CompletedStudy Start
First participant enrolled
January 14, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2027
March 2, 2026
February 1, 2026
14.1 years
March 13, 2012
February 26, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Assessment of toxicity of escalating doses of LMP, BARF1 and EBNA1 T lymphocytes
To determine the safety of escalating doses of 2 intravenous injections of autologous or syngeneic rapid LMP, BARF1 and EBNA1 specific T-lymphocytes (VSTs) in patients with EBV-associated Hodgkin's Disease or non-Hodgkin's lymphoma or T/NK-lymphoproliferative disease and CAEBV.
8 weeks
Secondary Outcomes (2)
Determine survival and immune function of LMP/BARF1/EBNA1-specific cytotoxic T-lymphocyte lines
1 year
Assess anti-viral and anti-tumor effects of LMP/BARF1/EBNA1-specific EBVST
1 year
Study Arms (2)
EBV-specific T cells: A
EXPERIMENTALGroup 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: B
EXPERIMENTALGroup 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
Interventions
Patients may receive cells with or without lymphodepletion. Dose Level 3: 1 x 10\^8 cells/m2 + 2 x 10\^8 cells/m2
Patients may receive cells with or without lymphodepletion. Dose Level 3: 1 x 10\^8 cells/m2 + 2 x 10\^8 cells/m2
Eligibility Criteria
You may qualify if:
- 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
- EBV positive tumor (can be pending at this time)
- Weighs at least 12kg
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
- 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)
- In remission or with minimal residual disease status after autologous or syngeneic SCT. (Group B)
- EBV positive tumor
- 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).
- Patients with a creatinine less than or equal to 2x upper limit of normal for age
- Pulse oximetry of \> 90% on room air
- 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.
- Patients with a Karnofsky/Lansky score of greater than or equal to 50
- 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.
- Informed consent explained to, understood and signed by patient/guardian. Patient/guardian given copy of informed consent.
- +2 more criteria
You may not qualify if:
- \. Active infection with HIV, HTLV, HBV, HCV (can be pending at this time)
- Pregnant or lactating
- Severe intercurrent infection.
- Current use of systemic corticosteroids \> 0.5 mg/kg/day
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Baylor College of Medicinelead
- The Methodist Hospital Research Institutecollaborator
- Center for Cell and Gene Therapy, Baylor College of Medicinecollaborator
- National Institutes of Health (NIH)collaborator
- National Cancer Institute (NCI)collaborator
- Harris County Hospital Districtcollaborator
Study Sites (3)
Harris Health System (includes ben Taub General Hospital and Smith)
Houston, Texas, 77030, United States
Houston Methodist Hospital
Houston, Texas, 77030, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Related Publications (2)
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.
PMID: 39908567DERIVEDSharma 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.
PMID: 38640255DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Helen E Heslop, MD
Baylor College of Medicine
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
March 13, 2012
First Posted
March 16, 2012
Study Start
January 14, 2013
Primary Completion (Estimated)
March 1, 2027
Study Completion (Estimated)
July 1, 2027
Last Updated
March 2, 2026
Record last verified: 2026-02