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TerminatedNCT01274377Updated Jun 5, 2017

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

A Phase 1 interventional study of CMV Specific T Cell donor lymphocyte infusion in Cytomegalovirus Infections, sponsored by Nelson Chao. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-06-05.

Sponsored by Nelson Chao · Phase 1, Interventional, and Prevention

Phase
Phase 1
Study type
Interventional
Enrollment
5
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

This protocol will evaluate the safety of CMV specific T cell infusion following nonmyeloablative stem cell transplantation from 3-6/6 HLA matched donors as well as evaluate the efficacy of antigen specific T cell infusions in preventing CMV activation.

02

Conditions studied

  • Cytomegalovirus Infections

Keywords

  • nonmyeloablative allogeneic stem cell transplantation
  • cytomegalovirus
  • donor lymphocyte infusions
  • cytotoxic T lymphocyte
03

In context

Cytomegalovirus Infections

359 studies on the registry are indexed under Cytomegalovirus Infections; 59 are open to participants now.

This study's enrollment of 5 is below the median of 60 across 233 interventional studies indexed under Cytomegalovirus Infections.

Browse Cytomegalovirus Infections studies →

Lead sponsor

Nelson Chao is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Subjects who have undergone a non-myeloablative allogeneic transplant, using a 3-6/6 Human Leukocyte Antigen (HLA) matched related donor.
  2. Subjects must be CMV seropositive prior to transplant by CMV immune screen or CMV IgG or develop detectable disease by PCR in the post-transplant setting.
  3. Performance status must be Karnofsky 50-100%.
  4. Donor cellular engraftment of at least 2.5% from the non-myeloablative procedure and prior to the first infusion.
  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 tid 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

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 the same donor used for the non-myeloablative allogeneic transplant and 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 or CMV IgG positive.
  3. Donors will complete the Adult Donor History Questionnaire and have all laboratory studies included in the Donor Referral NTL Panel, CBC with auto or manual differential, and a Chemistry Panel within 7 days of scheduled collection procedure. Donors who were evaluated greater than 1 year prior for transplant collection will also have a history and Physical Exam, CXR, and EKG completed. 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.
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Study design

Phase
Phase 1
Primary purpose
Prevention
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
5 participants (actual)

Study arms

  • Experimental
    Recipients Using 3-5/6 Matched Donors

    There will be an equal number of subjects (10) 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 20 subjects on study.

    Biological: CMV Specific T Cell donor lymphocyte infusion

  • Experimental
    Recipients Using 6/6 Matched Donors

    There will be an equal number of subjects (10) receiving transplants from 3-5/6 HLA Matched Donors as those receiving transplants from 6/6 HLA Matched Donors for a total of 20 subjects on study.

    Biological: CMV Specific T Cell donor lymphocyte infusion

Interventions

  • BiologicalCMV Specific T Cell donor lymphocyte infusion

    Donor Lymphocyte Infusion (DLI)

    Also known as: Miltenyi Biotec

06

What researchers measure

Primary outcomes

  1. Safety of CMV Specific T cell infusion following Stem Cell Transplant

    Donor Lymphocyte Infusion (DLI) of CMV Specific T cell clones following nonmyeloablative allogeneic stem cell transplant for the prevention of CMV

    Time frame: 2 years

Secondary outcomes

  1. Efficacy of CMV-specific T cell infusion in terms of response, progression free survival, and overall survival

    The efficacy and its effect on survivability will be assessed.

    Time frame: 2 years

  2. Evaluate the recovery of immune function post engraftment with this regimen.

    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.

    Time frame: 2 years

07

Study locations

1 site
  • Duke University Medical Center
    Durham, North Carolina 27705, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 5, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT01274377
Lead sponsor
Nelson Chao
Responsible party
Nelson Chao (Professor of Medicine, Duke University) — Sponsor-investigator
First posted
Jan 11, 2011
Start date
Feb 2011
Primary completion
Feb 23, 2015
Completion
Oct 5, 2015
Last update
Jun 5, 2017

Study contacts

Nelson Chao, MD
principal investigator · Duke University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Jun 2017. You cannot join it, but the record below documents what was studied.

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