Description:
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.
Title
- Brief Title: Safety and Effectiveness of EBV-specific Cytotoxic T Cells for the Treatment for EBV Lymphomas or Other EBV-associated Malignancies
- Official Title: A Phase II Trial of EBV-Specific Cytotoxic T Cells for the Treatment of EBV Lymphomas or Other EBV-associated Malignancies
Clinical Trial IDs
- ORG STUDY ID:
18-315
- NCT ID:
NCT03988582
Conditions
- EBV Lymphomas
- EBV-associated Malignancies
Interventions
Drug | Synonyms | Arms |
---|
EBV-specific T-cells | | HCT (hematopoietic cell transplant) recipients |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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). | |
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). | |
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). | |
Eligibility Criteria
Inclusion Criteria:
- 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:
1. EBV+ malignancies
2. EBV viremia (as evidenced by two serial plasma EBV DNA assays) without EBV+
malignancy
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:
1. EBV+ malignancies
2. 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
A. 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.
B. 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:
1. Availability of EBV-CTLs generated specifically for the patient and demonstrated to be
restricted by a shared HLA-allele.
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 for patients aged >
16 years; Lansky score ≥ 20 for patients ≤ 16 years
3. 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
4. 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):
A. 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
5. Patient or patient's representative is willing and able to provide written informed
consent
Exclusion Criteria:
1. 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.
2. 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.
3. Need for vasopressor or ventilatory support, unless deemed to be caused by the
EBV-driven process which EBV-CTLs are intended to treat
4. Pregnancy
5. Female of childbearing potential or male with a female partner of childbearing
potential unwilling to use a highly effective method of contraception
6. Inability to comply with study procedures
7. Patients who have received allogenic cells from a donor other than their HCT or SOT
donor within 30 days.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | N/A |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | best overall response rate |
Time Frame: | 6 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Withdrawn |
Lead Sponsor: | Memorial Sloan Kettering Cancer Center |
Trial Keywords
- cytotoxic T cells
- HLA-haplotype
- 18-315
Last Updated
June 11, 2020