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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by New York Medical College
Sponsor:
Collaborators:
Children's Research Institute
Baylor College of Medicine
M.D. Anderson Cancer Center
Beckman Research Institute
Johns Hopkins University
Ohio State University
University of Utah
University of Michigan
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College
ClinicalTrials.gov Identifier:
NCT01636388
First received: June 26, 2012
Last updated: September 23, 2014
Last verified: September 2014
  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.


Condition Intervention Phase
Hodgkins Lymphoma
Biological: allogeneic donor derived LMP specific cytotoxic T-lymphocyte
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by New York Medical College:

Primary Outcome Measures:
  • Safety [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.

  • Toxicity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The number of 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 toxicity of this treatment.


Secondary Outcome Measures:
  • Feasibility [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 45
Study Start Date: January 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allogeneic Stem Cell Transplantation
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.
Biological: allogeneic donor derived LMP specific cytotoxic T-lymphocyte
LMP CTLs will be give at 3 timepoints post allogeneic stem cell transplantation around days 60 to 100, then 30 days apart for the next 2 infusions.

  Eligibility

Ages Eligible for Study:   up to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01636388

Contacts
Contact: Mitchell Cairo, MD 9145943065 mitchell_cairo@nymc.edu
Contact: Lauren Harrison, MSN 978-993-4372 lauren_harrison@nymc.edu

Locations
United States, New York
New York Medical College Recruiting
Vallhala, New York, United States, 10595
Contact: Mitchell S Cairo, MD    914-594-3650    mitchell_cairo@nymc.edu   
Contact: Lauren Harrison, MSN    6172857844    lauren_harrison@nymc.edu   
Sponsors and Collaborators
New York Medical College
Children's Research Institute
Baylor College of Medicine
M.D. Anderson Cancer Center
Beckman Research Institute
Johns Hopkins University
Ohio State University
University of Utah
University of Michigan
Investigators
Principal Investigator: Mitchell S Cairo, MD New York Medical College
  More Information

No publications provided

Responsible Party: Mitchell Cairo, Principal Investigator, New York Medical College
ClinicalTrials.gov Identifier: NCT01636388     History of Changes
Other Study ID Numbers: NYMC-553
Study First Received: June 26, 2012
Last Updated: September 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New York Medical College:
Relapsed Hodgkins Lymphoma
Refractory Hodgkins Lymphoma
Allogeneic Stem Cell Transplantation
Adoptive Immunotherapy
Cellular Therapy
Cytotoxic T cell lymphocytes

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 24, 2014