Clinical Trials /

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

NCT02057445

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.

Related Conditions:
  • Lymphoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

3rd Party LMP1/2-Specific Cytotoxic T Lymphocytes for EBV-Associated <span class="go-doc-concept go-doc-disease">Lymphoma</span>

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

    NCT ID: NCT02057445

    ORG ID: NYMC-561

    Trial Conditions

    Non-Hodgkins Lymphoma

    Hodgkins Lymphoma

    Lymphoproliferative Disorder

    Trial Interventions

    Drug Synonyms Arms
    EBV CTL's Recipient

    Trial 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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Recipient Experimental EBV+ patients will receive 3rd party LMP-CTLs for treatment of EBV infection and/or disease EBV CTL's
    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 g 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

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    To determine the safety of giving 3rd party EBV-CTLs

    To develop a third party bank of LMP-specific CTL

    Secondary Outcome Measures

    To measure the response rate

    Trial Keywords

    cellular therapy

    lymphoma

    lymphoproliferative disorder