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.
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
Interventions
Drug | Synonyms | Arms |
---|
allogeneic donor derived LMP specific cytotoxic T-lymphocyte | | Allogeneic 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
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. | - 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