Clinical Trials /

Allogeneic Stem Cell Transplantation With Adoptive Immunotherapy in Epstein-Barr Virus Positive Recurrent/Refractory Hodgkins Lymphoma

NCT01636388

Description:

The investigators intend to utilize reduced intensity conditioning and allogeneic stem cell transplant from EBV positive HLA matched sibling or unrelated adult donor combined with post AlloSCT allogeneic donor derived LMP specific cytotoxic T-lymphocyte (CTL) infusions in EBV positive patients with poor risk Hodgkin Lymphoma. One of three reduced intensity conditioning regimens predetermined at each institutional center of the Childhood, Adolescent and Young Adult Lymphoma Cell Therapy Consortium (LCTC) will be utilized for related or matched unrelated adult donor allogeneic transplant followed by donor LMP specific CTL infusion for three doses post AlloSCT. The investigators hypothesize that the addition of donor derived LMP specific CTLs will be safe and feasible.

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Allogeneic Stem Cell Transplantation With Adoptive Immunotherapy in Epstein-Barr Virus Positive Recurrent/Refractory Hodgkins Lymphoma
  • Official Title: A Multicenter Pilot Study of Reduced Intensity Allogeneic Stem Cell Transplantation Followed by Adoptive Cellular Immunotherapy With Donor Derived Latent Membrane Protein (LMP) Specific-CTLs in Patients With Epstein-Barr Virus (EBV)Positive Refractory or Recurrent Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: NYMC-553
  • NCT ID: NCT01636388

Conditions

  • Hodgkins Lymphoma

Interventions

DrugSynonymsArms
allogeneic donor derived LMP specific cytotoxic T-lymphocyteAllogeneic Stem Cell Transplantation

Purpose

The investigators intend to utilize reduced intensity conditioning and allogeneic stem cell transplant from EBV positive HLA matched sibling or unrelated adult donor combined with post AlloSCT allogeneic donor derived LMP specific cytotoxic T-lymphocyte (CTL) infusions in EBV positive patients with poor risk Hodgkin Lymphoma. One of three reduced intensity conditioning regimens predetermined at each institutional center of the Childhood, Adolescent and Young Adult Lymphoma Cell Therapy Consortium (LCTC) will be utilized for related or matched unrelated adult donor allogeneic transplant followed by donor LMP specific CTL infusion for three doses post AlloSCT. The investigators hypothesize that the addition of donor derived LMP specific CTLs will be safe and feasible.

Trial Arms

NameTypeDescriptionInterventions
Allogeneic Stem Cell TransplantationExperimentalReduced intensity conditioning and allogeneic stem cell transplant from EBV positive HLA matched sibling or unrelated adult donor combined with post AlloSCT allogeneic donor derived LMP specific cytotoxic T-lymphocyte (CTL) infusions in EBV positive patients with poor risk Hodgkin Lymphoma.
  • allogeneic donor derived LMP specific cytotoxic T-lymphocyte

Eligibility Criteria

        Inclusion Criteria:

        Patient must be 45 years of age or less.

        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 cardiac function defined as:

        Shortening fraction of >27% by echocardiogram

        Hodgkin Lymphoma with either of the following:

        Primary induction failure (failure to achieve initial CR) and/or primary refractory
        disease.First relapse ; Early relapse (within 12 months off therapy) (excluding those who
        received no therapy or radiation therapy only for initial therapy); Late relapse (greater
        than 12 months off therapy). Only patients with recurrent Stage III or IV disease and/or
        those with B symptoms at relapse (all other late relapses are excluded); Second relapse;
        Third relapse.

        History of prior ablative auto HSCT or ineligible for an ablative auto HSCT or ≥25%
        residual disease after at least two reinduction chemotherapy cycles.

        EBV seropositive IgG HLA matched family or unrelated donor (MUD) HLA matched family donor
        (6/6 or 5/6) or matched unrelated adult donor (MUD) (7/8 or 8/8) All patients entered into
        the study ideally will have tumor tissue from the original diagnostic specimen and/or
        relapse reviewed centrally for confirmation of Hodgkin lymphoma. 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.

        Exclusion Criteria:

        Patients with HD with 4th or greater CR, PR, and/or SD are ineligible. Patients with
        rapidly progressive disease (PD) unresponsive to reinduction chemo, radio, or immunotherapy
        are ineligible.

        EBV negative Hodgkin Lymphoma. Patients who don't have an eligible donor (outlined in 7.0)
        are ineligible. Women who are pregnant are ineligible. Negative pregnancy test in women of
        childbearing age is required.
      
Maximum Eligible Age:45 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety
Time Frame:1 year
Safety Issue:
Description:The number of serious adverse events associated with administering allogeneic HLA matched donor derived LMP specific-CTLs in CAYA with EBV-associated refractory/relapsed HL following reduced intensity conditioning (RIC) and allogeneic HSCT will be monitored to determine the safety of this treatment.

Secondary Outcome Measures

Measure:Feasibility
Time Frame:1 year
Safety Issue:
Description:Good Manufacturing Practice (GMP) production and shipping of HLA matched donor derived LMP specific-CTLs to multiple sites in various geographic regions of the US following RIC and allogeneic HSCT will be monitored to assess the feasibility.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:New York Medical College

Trial Keywords

  • Relapsed Hodgkins Lymphoma
  • Refractory Hodgkins Lymphoma
  • Allogeneic Stem Cell Transplantation
  • Adoptive Immunotherapy
  • Cellular Therapy
  • Cytotoxic T cell lymphocytes

Last Updated

December 22, 2017