Trial of CMV Specific DLIs From 3-6/6 HLA Matched Family Member Following Nonmyeloablative Allo SCT

This study is currently recruiting participants.
Verified December 2013 by Duke University
Sponsor:
Information provided by (Responsible Party):
Nelson Chao, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01274377
First received: January 9, 2011
Last updated: December 27, 2013
Last verified: December 2013
  Purpose

Human cytomegalovirus (CMV) is a benign infectious agent in the normal host, but in immunocompromised individuals, such as recipients of stem cell transplants, this virus is a major cause of morbidity and mortality. While pharmacologic agents exist to treat CMV disease, these medications have numerous side effects, the most serious of which is myelosuppression. The frequency of neutropenia ranges from 41% to 58% in stem cell transplant (SCT) patients treated with ganciclovir. Withdrawal of anti-CMV therapy due to these complications may result in recurrent disease. The restoration of cellular immunity to CMV is necessary in order to prevent viral reactivation, and the generation of cytotoxic T cells against CMV early antigens is perhaps the most important part of the host immune response to CMV. At day 40 post-transplant, for example, at least 65% of SCT patients are deficient in CD8+ T-cell responses to CMV. Previous studies have demonstrated a direct correlation between CMV infection in these patients and cytotoxic T lymphocyte (CTL) function, with patients who have defects in cellular immunity being at high risk for invasive CMV disease. The median time post-transplant for the development of CMV disease is 50 to 60 days, and CMV re-activation occurs in 70 to 80% of CMV sero-positive SCT recipients. Without anti-viral therapy as many as 50% of these patients will develop CMV disease.


Condition Intervention Phase
Cytomegalovirus Infections
Biological: CMV Specific T Cell donor lymphocyte infusion
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase I Trial of CMV Specific Donor Lymphocyte Infusions From 3-6/6 HLA Matched Family Member Following Nonmyeloablative Allogeneic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Safety of CMV Specific T cell infusion following Stem Cell Transplant [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Donor Lymphocyte Infusion (DLI) of CMV Specific T cell clones following nonmyeloablative allogeneic stem cell transplant for the prevention of CMV


Secondary Outcome Measures:
  • Efficacy of CMV-specific T cell infusion in terms of response, progression free survival, and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    The efficacy and its effect on survivability will be assessed.

  • Evaluate the recovery of immune function post engraftment with this regimen. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Blood samples will be collected for immune reconstitution studies, including assessing CMV specific responses, just prior to each cell infusion, and 3,6, 12 months post last infusion.


Estimated Enrollment: 32
Study Start Date: February 2011
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Recipients Using 3-5/6 Matched Donors
There will be an equal number of subjects (16) receiving transplants from 3-5/6 Human Leukocyte Antigen (HLA) Matched Donors as those receiving transplants from 6/6 HLA Matched Donors for a total of 32 subjects on study.
Biological: CMV Specific T Cell donor lymphocyte infusion
Donor Lymphocyte Infusion (DLI)
Other Name: Miltenyi Biotec
Experimental: Recipients Using 6/6 Matched Donors
There will be an equal number of subjects (16) receiving transplants from 3-5/6 HLA Matched Donors as those receiving transplants from 6/6 HLA Matched Donors for a total of 32 subjects on study.
Biological: CMV Specific T Cell donor lymphocyte infusion
Donor Lymphocyte Infusion (DLI)
Other Name: Miltenyi Biotec

Detailed Description:

This protocol will evaluate the safety of CMV specific T cell infusion following nonmyeloablative stem cell transplantation from matched or mismatched donors as well as evaluate the efficacy of antigen specific T cell infusions in preventing CMV activation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects who have undergone a non-myeloablative allogeneic transplant, using a 3-6/6 Human Leukocyte Antigen (HLA) matched related donor. Measureable disease is not needed at study entry.
  2. Subjects must be CMV seropositive prior to transplant by CMV immune screen.
  3. Performance status must be Karnofsky 50-100%.
  4. Donor cellular engraftment of at least 2.5% from the non-myeloablative procedure.
  5. ≤ Grade 1 acute graft versus host disease (GVHD) at time of the CMV specific T cell infusion. Patients with treated acute GVHD must be on a stable dose of therapy (no increase in immunosuppressive therapy for the 2 weeks before planned donor cell infusion). The dosage level of immunosuppressive therapy at the time of infusion should be no greater than 20 mg of prednisone daily or mycophenolate 1000 mg bid daily or cyclosporine with a target level of 200 ng/ml or equivalent.
  6. At the time of the CMV specific T cell infusion, the recipient must have adequate organ function as indicated by < Grade 3 across all organ systems except for hematologic toxicity.
  7. Subject must be at least 18 years of age.

Exclusion Criteria:

  1. Pregnant or lactating women,
  2. Subjects with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise compliance with this protocol.
  3. Subjects who had histopathologically confirmed overall Grade 4 GVHD lasting longer than 7 days, from the non-myeloablative therapy, are not eligible.

Donor Inclusion/Exclusion Criteria

  1. Adult donors must be must be a related family member with a HLA 3-6/6 match with the subject and must be capable of providing informed consent; Potential donors under the age of 18 must have a 'single patient exemption' approved by the Institutional Review Board (IRB) and the donor and a guardian must provide assent. The donor must be the same donor used for the original allogeneic transplantation. Selection of donors will be compliant with 21 CFR 1271.
  2. Adult donors must be CMV seropositive prior to transplant by CMV immune screen.
  3. Family members will be considered for donation if they do not have a history of known cardiac problem and do not have abnormal cardiac findings by physical examination. Those with a history of cardiac problems or abnormal cardiac findings by physical examination should undergo a stress evaluation or be evaluated by a cardiologist and deemed eligible to donate. Donors must not have any medical condition which would make apheresis more than a minimal risk, and should have normal range laboratory findings. All abnormal laboratory findings will be evaluated by the treating physician within the context of the entire donor assessment process.
  4. Females of childbearing potential should have a negative serum beta-HCG (human chorionic gonadotropin) test within 1 week of beginning apheresis.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01274377

Contacts
Contact: Gwynn Long, MD (919) 668-7395 gwynn.long@duke.edu
Contact: Krista Rowe, RN (919) 684-7115 Krista.Rowe@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27705
Contact: Nelson Chao, MD    919-668-1002    chao0002@mc.duke.edu   
Contact: Gwynn Long, MD    919-668-7395    gwynn.long@duke.edu   
Sub-Investigator: Gwynn Long, MD         
Sub-Investigator: David Rizzieri, MD         
Sub-Investigator: Mitchell Horwitz, MD         
Sub-Investigator: Cristina Gasparetto, MD         
Sub-Investigator: Keith Sullivan, MD         
Sub-Investigator: John Chute, MD         
Principal Investigator: Nelson Chao, MD         
Sponsors and Collaborators
Nelson Chao
Investigators
Principal Investigator: Nelson Chao, MD Duke University
  More Information

No publications provided

Responsible Party: Nelson Chao, Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01274377     History of Changes
Other Study ID Numbers: Pro00013947
Study First Received: January 9, 2011
Last Updated: December 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
nonmyeloablative allogeneic stem cell transplantation
cytomegalovirus
donor lymphocyte infusions
cytotoxic T lymphocyte

Additional relevant MeSH terms:
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on April 21, 2014