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

Allogeneic <span class="go-doc-concept go-doc-intervention">Stem Cell</span> Transplantation With <span class="go-doc-concept go-doc-intervention">Adoptive Immunotherapy</span> in Epstein-Barr Virus Positive Recurrent/Refractory Hodgkins <span class="go-doc-concept go-doc-disease">Lymphoma</span>

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

    NCT ID: NCT01636388

    ORG ID: NYMC-553

    Trial Conditions

    Hodgkins Lymphoma

    Trial Interventions

    Drug Synonyms Arms

    Trial 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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Allogeneic Stem Cell Transplantation Experimental 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.

    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.

    Minimum Eligible Age: N/A

    Maximum Eligible Age: 45 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Safety

    Toxicity

    Secondary Outcome Measures

    Feasibility

    Trial Keywords

    Relapsed Hodgkins Lymphoma

    Refractory Hodgkins Lymphoma

    Allogeneic Stem Cell Transplantation

    Adoptive Immunotherapy

    Cellular Therapy

    Cytotoxic T cell lymphocytes