Description:
The administration of allogeneic third party derived LMP specific-CTLs (special peripheral
blood cells from another person) that are made specific to fight EBV infection) in Children,
Adolescents and Young Adults (CAYA) with EBV-associated refractory or relapsed lymphoma will
be feasible ( able to be done), safe and well tolerated (no unexpected serious events will
occur). In addition, potential donors who are EBV positive will be enrolled to donate
peripheral blood to help build a bank of these specific EBV fighting cell lines.
Title
- Brief Title: 3rd Party LMP1/2-Specific Cytotoxic T Lymphocytes for EBV-Associated Lymphoma
- Official Title: A Multicenter Pilot Study of Third Party LMP1/2-Specific Cytotoxic T Lymphocytes for Treatment of Patients With Refractory /Relapsed EBV-Associated Lymphoma A Childhood, Adolescent and Young Adult Lymphoma Cell Therapy Consortium (LCTC) Multicenter Clinical Trial
Clinical Trial IDs
- ORG STUDY ID:
NYMC-561
- NCT ID:
NCT02057445
Conditions
- Non-Hodgkins Lymphoma
- Hodgkins Lymphoma
- Lymphoproliferative Disorder
Interventions
Drug | Synonyms | Arms |
---|
EBV CTL's | | Recipient |
Purpose
The administration of allogeneic third party derived LMP specific-CTLs (special peripheral
blood cells from another person) that are made specific to fight EBV infection) in Children,
Adolescents and Young Adults (CAYA) with EBV-associated refractory or relapsed lymphoma will
be feasible ( able to be done), safe and well tolerated (no unexpected serious events will
occur). In addition, potential donors who are EBV positive will be enrolled to donate
peripheral blood to help build a bank of these specific EBV fighting cell lines.
Trial Arms
Name | Type | Description | Interventions |
---|
Recipient | Experimental | EBV+ patients will receive 3rd party LMP-CTLs for treatment of EBV infection and/or disease | |
Donor | Other | Healthy donors who are EBV+ will be asked to donate 60-120 ml of peripheral blood for development of cell lines to be stored for cell line bank. | |
Eligibility Criteria
Inclusion Criteria:
Patient must be at least 1 year of age.
Patient or the patient's legally authorized guardian must be fully informed about their
illness and the investigational nature of the study protocol (including foreseeable risks
and possible side effects), and must sign an informed consent in accordance with the
institutional policies approved by the U.S. Department of Health and Human Services.
Patients should have been off other investigational therapy for one month prior to entry in
this study.
Patient must have adequate organ function as below:
Adequate renal function defined as:
- Serum creatinine <2.0 x normal, or
- Creatinine clearance or radioisotope GFR > 40 ml/min/m2 or >60 ml/min/1.73 m2 or an
equivalent GFR as determined by the institutional normal range
Adequate liver function defined as:
- Total bilirubin <2.0 x normal; and
- SGOT (AST) or SGPT (ALT) <5.0 x normal
Adequate pulmonary function defined as:
- Pulse oximetry >94% in room air. Lansky (< 16yr) or Karnofsky (> 16 yrs) performance
status ≥ 50% Life expenctancy ≥ 6 weeks. Women of child bearing age require a negative
urine pregnancy test. Clinical status at enrollment to allow tapering of steroids to less
than 0.5mg/kg/day prednisone at time of treatment.
4.5 Disease Status (Eligibility) 4.5.1 Any patient, with one or more of the following
EBV-positive type II latency or associated disorders, regardless of the histological
subtype: Hodgkin lymphoma Non-Hodgkin lymphoma Lymphoproliferative disorder Severe chronic
active EBV infection syndrome (SCAEBV), defined as high EBV viral load in plasma or PBMC (>
4000 genomes per μg PBMC DNA) and/or biopsy tissue positive for EBV
The disease needs to be in one of the following stages:
At diagnosis who would be unable to receive conventional chemotherapy or in first relapse
AND the patient is not a candidate for HSCT Partial response after conventional therapy.
Refractory to conventional therapy for his/her condition. In second or subsequent relapse.
Residual disease after autologous, syngeneic or allogeneic HSCT.
All patients entered into the study ideally will have tumor tissue from the original
diagnostic specimen and/or relapse reviewed centrally for confirmation of EBV positive
disease. If no specimen is available, local pathology report documenting EBV positivity is
acceptable. Appropriate immunophenotyping to confirm the diagnosis will be performed. In
addition, in situ hybridization for EBV (LMP1, and/or EBER positivity) will be performed.
All central morphologic analysis and immunohistochemical/insitu hybridization staining will
be performed in the laboratory of Sherrie Perkins and Rodney Miles at the University of
Utah.
Donor Eligibility for LMP-CTL Third Party Banking (Aim 2.1.2)
- Donor must be HIV negative.
- Donors must have adequate hematopoietic function defined as absolute neutrophil count
> 1000/mm3, hemoglobin > 10 g/dl, and platelet count >50,000/mm3 and be EBV IgG
seropositive.
- Donors will have peripheral blood collected for LMP specific CTL production. A minimum
of 60 cc of peripheral blood x 2 for a total maximum amount of blood of 120cc, will be
collected from the donor (subjects must be at least 12 kg or 24 pounds). (See Appendix
B) For donors <18 years a maximum of 3cc/kg blood will be taken in an 8 week period.
- For donors that are to undergo stem cell collection, the peripheral blood for LMP
specific CTL production will be collected prior to the stem cell collection and
without a specific day specification.
- Donor eligibility must meet criteria as per 21 CFR 1271.
Exclusion Criteria:
Currently receiving any investigational agents or have received any tumor vaccines within
previous 4 weeks.
Active acute grade III-IV graft-versus-host disease. Severe refractory intercurrent
infection other than EBV. Received alemtuzumab or other anti-Tcell antibody within 28 days.
HIV seropositivity. Pregnancy (due to unknown effects of this therapy on a fetus) or
lactation. Patients with PTLD post solid organ transplantation eligible for the COG PTLD
LMP/CTL protocol.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 1 Year |
Eligible Gender: | All |
Healthy Volunteers: | Accepts Healthy Volunteers |
Primary Outcome Measures
Measure: | To determine the safety of giving 3rd party EBV-CTLs |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Patients will be monitored for any unexpected adverse events related to investigational product. |
Secondary Outcome Measures
Measure: | To measure the response rate |
Time Frame: | 1 year |
Safety Issue: | |
Description: | patients will be followed a year following administration of cells for disease response. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | New York Medical College |
Trial Keywords
- cellular therapy
- lymphoma
- lymphoproliferative disorder
Last Updated
December 22, 2017