search
Back to results

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

Primary Purpose

Hodgkins Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
allogeneic donor derived LMP specific cytotoxic T-lymphocyte
Sponsored by
New York Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hodgkins Lymphoma focused on measuring Relapsed Hodgkins Lymphoma, Refractory Hodgkins Lymphoma, Allogeneic Stem Cell Transplantation, Adoptive Immunotherapy, Cellular Therapy, Cytotoxic T cell lymphocytes

Eligibility Criteria

undefined - 45 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • New York Medical College

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Allogeneic Stem Cell Transplantation

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety
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
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
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.

Full Information

First Posted
June 26, 2012
Last Updated
December 20, 2017
Sponsor
New York Medical College
Collaborators
Children's National Research Institute, Baylor College of Medicine, M.D. Anderson Cancer Center, City of Hope Medical Center, Johns Hopkins University, Ohio State University, University of Utah, University of Michigan
search

1. Study Identification

Unique Protocol Identification Number
NCT01636388
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Why Stopped
funding ended
Study Start Date
January 2013 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York Medical College
Collaborators
Children's National Research Institute, Baylor College of Medicine, M.D. Anderson Cancer Center, City of Hope Medical Center, Johns Hopkins University, Ohio State University, University of Utah, University of Michigan

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkins Lymphoma
Keywords
Relapsed Hodgkins Lymphoma, Refractory Hodgkins Lymphoma, Allogeneic Stem Cell Transplantation, Adoptive Immunotherapy, Cellular Therapy, Cytotoxic T cell lymphocytes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Allogeneic Stem Cell Transplantation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
allogeneic donor derived LMP specific cytotoxic T-lymphocyte
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety
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.
Time Frame
1 year
Title
Toxicity
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Feasibility
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.
Time Frame
1 year

10. Eligibility

Sex
All
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mitchell S Cairo, MD
Organizational Affiliation
New York Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs