EBV LymphomasPhase 2NCT03988582
Safety and Effectiveness of EBV-specific Cytotoxic T Cells for the Treatment for EBV Lymphomas or Other EBV-associated Malignancies
A Phase 2 study testing EBV-specific T-cells in people with EBV Lymphomas and EBV-associated Malignancies, run by Memorial Sloan Kettering Cancer Center.
Trial summary
The purpose of this study is to test whether treatment with EBV-specific cytotoxic T cells (EBV-CTLs) is effective, and to test any good and bad effects of treatment with EBV-CTLs. EBV-CTLs are a special immune cells that may attack abnormal cells. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- EBV Lymphomas, EBV-associated Malignancies
- What is being tested?
- EBV-specific T-cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 11 Jun 2019to 8 Jun 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- A patient will be considered eligible to receive EBV-CTL treatment if the following inclusion criteria are met. Patients should receive established effective therapy if it exists and they can tolerate it prior to enrolling on protocol to receive experimental therapy. Patients will be considered eligible regardless of initial response to rituximab (alloHCT recipients) rituximab and/or multi-agent chemotherapy (SOT and other immune compromised recipients) and appropriate first line chemotherapy (non immune compromised recipients).
- Three cohorts of patients will be eligible for enrollment:
- °Cohort 1
- Patients after allogeneic HCT who have:
- EBV+ malignancies
- EBV viremia (as evidenced by two serial plasma EBV DNA assays) without EBV+ malignancy
Show all 33Show fewer
- Included in cohort 1 will be patients with underlying immunodeficiency syndromes with:
- 3. EBV+ malignancies 4. EBV viremia without current but with a history of prior EBV+ malignancy
- Cohort 2
- Patients after allogeneic SOT who have:
- EBV+ malignancies
- EBV viremia (as evidenced by two serial plasma EBV DNA assays) without current but with a history of prior EBV+ malignancy.
- Patients in Cohort 1 (D) and 2 (B) treated for EBV viremia without evidence of EBV+ malignancy will need to have a history of a prior EBV malignancy with:
- Continued viremia at the completion of planned therapy
- Recurrence of viremia within 2 months from completion of planned therapy
- High grade viremia (>20,000 copies) after treatment for EBV malignancy
- Evidence of EBV positivity for patients in cohort 1 and 2 is determined as follows:
- A biopsy showing EBV+ malignancy or
- A combination of EBV viremia AND radiographic appearance consistent with an EBV+ malignancy
- Cohort 3
- EBV-associated lymphomas and lymphoproliferative disorders not associated with immunodeficiency (biopsy required) (e.g. EBV+ Hodgkin lymphoma, etc).
- Based on prior studies, patients with NK/T lymphoma will only be eligible for protocol if EBV-CTL therapy is being administered from their HCT donor either prior to or after HCT.
- Other EBV-associated malignancies (biopsy required) including nasopharyngeal carcinoma, EBV+ gastric cancer, EBV+ leiomyosarcoma.
- Patients in cohort 3 will be assessed for whether alternative standard therapy is available prior to being consented to the trial.
- Patients in cohort 3 will need a biopsy showing EBV+ disease.
- Patients in cohort 3 will not be treated for viremia alone.
- All Patients:
- Availability of EBV-CTLs generated specifically for the patient and demonstrated to be restricted by a shared HLA-allele.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 for patients aged > 16 years; Lansky score ≥ 20 for patients ≤ 16 years
- For patients with PTLD in the alloHCT setting, the underlying disease for which alloHCT transplant was performed is either an EBV+ malignancy or in morphologic remission
- Adequate organ function per the following (unless deemed to be caused by the underlying EBV-driven process which EBV-CTLs are intended to treat, or its prior therapy):
- Absolute neutrophil count ≥ 500/μL, with or without cytokine support B. Platelet count ≥ 20,000/μL, with or without transfusion support C. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3× the upper limit of normal (ULN) and total bilirubin < 2.5×ULN; D. Creatinine < 3×ULN
- Patient or patient's representative is willing and able to provide written informed consent
Who cannot join
- Any concomitant investigational therapy that would impair the ability to assess efficacy or toxicity of the EBV-CTL treatment. Simultaneous initiation of rituximab therapy in a patient who has received no prior rituximab.
- Uncontrolled graft versus host disease or organ rejection or ongoing need for methotrexate, extracorporeal photopheresis, or corticosteroids at a dose greater than 0.5mg/kg/day prednisone or equivalent.
- Need for vasopressor or ventilatory support, unless deemed to be caused by the EBV-driven process which EBV-CTLs are intended to treat
- Pregnancy
- Female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
- Inability to comply with study procedures
- Patients who have received allogenic cells from a donor other than their HCT or SOT donor within 30 days.
About this study
Official title: A Phase II Trial of EBV-Specific Cytotoxic T Cells for the Treatment of EBV Lymphomas or Other EBV-associated Malignancies
The purpose of this study is to test whether treatment with EBV-specific cytotoxic T cells (EBV-CTLs) is effective, and to test any good and bad effects of treatment with EBV-CTLs. EBV-CTLs are a special immune cells that may attack abnormal cells. EBV-CTLs are made by taking cells from a healthy person, growing them in a laboratory for several weeks to educate them to recognize and destroy EBV infected cells, and then storing them in a freezer until they are required for treatment.
- Conditions
- EBV Lymphomas, EBV-associated Malignancies
- Being tested
- EBV-specific T-cells
- Keywords
- cytotoxic T cells, HLA-haplotype, 18-315
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EBV-specific T-cellsBiological
During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period.
| Study group | Role | What they receive |
|---|---|---|
| HCT (hematopoietic cell transplant) recipients | Experimental | EBV-CTLs will be administered in cycles lasting 5 weeks (35 days). During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period. Each dose, or the cumulative three doses can be within 20% of the targeted dose.Treatment will continue until maximal response, unacceptable toxicity, or failure of EBV-CTLs (progression of disease after three cycles of cells or 6 months of therapy without response). Receives: Biological: EBV-specific T-cells |
| SOT (solid organ transplant) recipients | Experimental | EBV-CTLs will be administered in cycles lasting 5 weeks (35 days). During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period. Each dose, or the cumulative three doses can be within 20% of the targeted dose.Treatment will continue until maximal response, unacceptable toxicity, or failure of EBV-CTLs (progression of disease after three cycles of cells or 6 months of therapy without response). Receives: Biological: EBV-specific T-cells |
| Other immune competent or immune compromised patients | Experimental | EBV-CTLs will be administered in cycles lasting 5 weeks (35 days). During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period. Each dose, or the cumulative three doses can be within 20% of the targeted dose.Treatment will continue until maximal response, unacceptable toxicity, or failure of EBV-CTLs (progression of disease after three cycles of cells or 6 months of therapy without response). Receives: Biological: EBV-specific T-cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
best overall response rate
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2019
- Study start11 Jun 2019
- Primary completion8 Jun 2020
- Study completion8 Jun 2020
Why it stopped: Lack of accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EBV LymphomasStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susan Prockop, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03988582
- Sponsor's protocol ID
- 18-315
- Status last verified
- Jun 2020
- First submitted
- 13 Jun 2019
- Last updated
- 11 Jun 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of EBV-Specific Cytotoxic T Cells for the Treatment of EBV Lymphomas or Other EBV-associated Malignancies
- ClinicalTrials.gov ID
- NCT03988582
- Acronym / sponsor ID
- 18-315
- Conditions
- EBV Lymphomas, EBV-associated Malignancies
- Keywords
- cytotoxic T cells, HLA-haplotype, 18-315
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 11 Jun 2019 (actual)
- Primary completion
- 8 Jun 2020 (actual)
- Study completion
- 8 Jun 2020 (actual)
- First posted
- 17 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test whether treatment with EBV-specific cytotoxic T cells (EBV-CTLs) is effective, and to test any good and bad effects of treatment with EBV-CTLs. EBV-CTLs are a special immune cells that may attack abnormal cells. EBV-CTLs are made by taking cells from a healthy person, growing them in a laboratory for several weeks to educate them to recognize and destroy EBV infected cells, and then storing them in a freezer until they are required for treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HCT (hematopoietic cell transplant) recipients | Experimental | Biological: EBV-specific T-cellsEBV-CTLs will be administered in cycles lasting 5 weeks (35 days). During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period. Each dose, or the cumulative three doses can be within 20% of the targeted dose.Treatment will continue until maximal response, unacceptable toxicity, or failure of EBV-CTLs (progression of disease after three cycles of cells or 6 months of therapy without response). |
| SOT (solid organ transplant) recipients | Experimental | Biological: EBV-specific T-cellsEBV-CTLs will be administered in cycles lasting 5 weeks (35 days). During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period. Each dose, or the cumulative three doses can be within 20% of the targeted dose.Treatment will continue until maximal response, unacceptable toxicity, or failure of EBV-CTLs (progression of disease after three cycles of cells or 6 months of therapy without response). |
| Other immune competent or immune compromised patients | Experimental | Biological: EBV-specific T-cellsEBV-CTLs will be administered in cycles lasting 5 weeks (35 days). During each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period. Each dose, or the cumulative three doses can be within 20% of the targeted dose.Treatment will continue until maximal response, unacceptable toxicity, or failure of EBV-CTLs (progression of disease after three cycles of cells or 6 months of therapy without response). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (33 listed)
- A patient will be considered eligible to receive EBV-CTL treatment if the following inclusion criteria are met. Patients should receive established effective therapy if it exists and they can tolerate it prior to enrolling on protocol to receive experimental therapy. Patients will be considered eligible regardless of initial response to rituximab (alloHCT recipients) rituximab and/or multi-agent chemotherapy (SOT and other immune compromised recipients) and appropriate first line chemotherapy (non immune compromised recipients).
- Three cohorts of patients will be eligible for enrollment:
- °Cohort 1
- Patients after allogeneic HCT who have:
- 3. EBV+ malignancies 4. EBV viremia without current but with a history of prior EBV+ malignancy
Key exclusion criteria (7 listed)
- Any concomitant investigational therapy that would impair the ability to assess efficacy or toxicity of the EBV-CTL treatment. Simultaneous initiation of rituximab therapy in a patient who has received no prior rituximab.
- Uncontrolled graft versus host disease or organ rejection or ongoing need for methotrexate, extracorporeal photopheresis, or corticosteroids at a dose greater than 0.5mg/kg/day prednisone or equivalent.
- Need for vasopressor or ventilatory support, unless deemed to be caused by the EBV-driven process which EBV-CTLs are intended to treat
- Pregnancy
- Female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EBV-specific T-cellsDuring each cycle, patients will receive intravenous (IV) EBV-CTLs at a dose of 1×106 CD3+ cells/kg on Days 1, 8, and 15, followed by a 2-week observation period. | Biological | HCT (hematopoietic cell transplant) recipients, Other immune competent or immune compromised patients, SOT (solid organ transplant) recipients |
Primary outcome
best overall response rate
Time frame: 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2020.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan Prockop, MD principal investigator
Memorial Sloan Kettering Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EBV-specific T-cells in people with EBV Lymphomas and EBV-associated Malignancies, run by Memorial Sloan Kettering Cancer Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
best overall response rate (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2020.