3rd Party LMP1/2-Specific Cytotoxic T Lymphocytes for EBV-Associated Lymphoma

NCT ID: NCT02057445

Last Updated: 2017-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

1 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2017-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Non-Hodgkins Lymphoma Hodgkins Lymphoma Lymphoproliferative Disorder

Keywords

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cellular therapy lymphoma lymphoproliferative disorder

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Recipient

EBV+ patients will receive 3rd party LMP-CTLs for treatment of EBV infection and/or disease

Group Type EXPERIMENTAL

EBV CTL's

Intervention Type DRUG

Eligible patients with a matched cell line will be infused with 3rd party CTLs and monitored for adverse events and response. Patients who show a response and tolerate the infusion well may receive up to 5 infusions total 4-6 weeks apart.

Donor

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.

Group Type OTHER

Peripheral Blood Donor

Intervention Type OTHER

Donors who are EBV+ and meet the eligibility criteria will be consented to provide 60-120 ml peripheral blood once for future use for this and other clinical trials using 3rd party CTLs.

Interventions

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EBV CTL's

Eligible patients with a matched cell line will be infused with 3rd party CTLs and monitored for adverse events and response. Patients who show a response and tolerate the infusion well may receive up to 5 infusions total 4-6 weeks apart.

Intervention Type DRUG

Peripheral Blood Donor

Donors who are EBV+ and meet the eligibility criteria will be consented to provide 60-120 ml peripheral blood once for future use for this and other clinical trials using 3rd party CTLs.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Children's National Research Institute

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role collaborator

City of Hope Medical Center

OTHER

Sponsor Role collaborator

Ohio University

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

New York Medical College

OTHER

Sponsor Role lead

Responsible Party

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Mitchell Cairo

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mitchell Cairo, MD

Role: PRINCIPAL_INVESTIGATOR

New York Medical College

Catherine Bollard, MD

Role: PRINCIPAL_INVESTIGATOR

Children's National Research Institute

Locations

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Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Countries

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United States

Other Identifiers

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NYMC-561

Identifier Type: -

Identifier Source: org_study_id