Cytomegalovirus (CMV) Specific Cytotoxic T Lymphocytes (CTL) When Used for Prophylaxis Against CMV in Recipients of Allogeneic, T Cell Depleted Stem Cell Transplants

This study has been completed.
Sponsor:
Information provided by:
Penn State University
ClinicalTrials.gov Identifier:
NCT00673868
First received: May 1, 2008
Last updated: January 22, 2009
Last verified: April 2008
  Purpose

This study examines the immunologic and virologic effects of prophylactic CMV specific CTL in recipients of T cell depleted stem cell transplant (TCD SCT) at Duke University Medical Center (DUMC), by measuring levels of CMV DNA and virus specific T cell precursors at intervals post-infusion.


Condition Intervention Phase
Cytomegalovirus Infections
Other: CMV Specific Cytotoxic T Lymphocytes
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I-II Randomized Trial to Examine the Clinical, Immunologic and Virologic Effects of CMV Specific CTL When Used for Prophylaxis Against CMV Disease in Recipients of Allogeneic, T Cell Depleted Stem Cell Transplants

Resource links provided by NLM:


Further study details as provided by Penn State University:

Primary Outcome Measures:
  • The primary objective is to characterize CMV specific immunity in subjects receiving and in those randomized to not receive CMV CTL. We will characterize CMV CTLp frequencies and bulk cytotoxicity at days 30 and 60 post infusion. [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To characterize the time to develop CMV specific immunity in pts. receiving and not receiving CTL by assessing CMV CTL [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • To determine the CMV epitopes recognized by donors [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • To characterize the levels of CMV DNA in recipients of CMV CTL and non CTL [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 47
Study Start Date: October 2007
Arms Assigned Interventions
Experimental: 1 Other: CMV Specific Cytotoxic T Lymphocytes
CMV Specific Cytotoxic T Lymphocytes will be infused between days 30 and 40 post-transplant at a dose ranging from 2- 5 x e5 cells/kg.
No Intervention: 2

Detailed Description:

Human cytomegalovirus (CMV) is a benign infectious agent in the normal host, but in immunocompromised individuals, such as recipients of stem cell or organ 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. Considering the risk associated with persistent infection and the potential for CMV specific CTL to restore immunity, we propose to study the immunologic and virologic effects of CMV pp65 specific CTL given to SCT recipients prophylactically, levels of CMV pp65 specific CTL and CMV DNA will be measured from CTL recipients and a control group randomized to not receive CTL.

All treatments will be given at Duke University Medical Center (DUMC).

  1. Patients will have a complete set of vital signs and physical examination prior to each infusion. Pulse oximetry will be monitored prior to, during, and for 30 minutes after the T-cell infusion. Thirty minutes prior to the CTL infusion, patients will be pre-medicated with 15 mg/kg (maximum 1 g) of acetaminophen p.o. and 1.0 mg/kg diphenhydramine I.V. (maximum 50 mg). Cells will be thawed in the Cell Therapy lab at DUMC, an aliquot sent for gram stain and culture, and viability will be determined. Cells with > 70 % viability will be transferred to the clinical unit and infused over 5-10 minutes.
  2. CMV CTL will be infused when available between days 30 and 40 post-transplant at a dose ranging from 2- 5 x 105 cells/kg. This dose range was established since there may be variability in the numbers of CTL expanded from these donors.
  Eligibility

Ages Eligible for Study:   2 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Any allogeneic stem cell transplant recipient > 2 years of age who is CMV sero-positive and has a CMV sero-positive donor,
  • Bilirubin < 2.0 mg/dl; SGOT/SGPT < 2.5 X normal.
  • Creatinine clearance > 50 cc/min as estimated by patient's serum creatinine, weight, and age.
  • Pulse oximetry > 95% on no supplemental oxygen.
  • ECOG performance status < 2; for patients, 16 years of age, Lansky performance status >70%.

Exclusion Criteria:

  • Sero-negative patients with a history of GVHD of grade II or greater by the Glucksberg crireria (protocol Appendix I) at or prior to day +30 of current stem cell transplant are excluded.
  • Patients who have received a prior stem cell transplant are excluded.
  • Patients who are moribund or who because of cardiac, pulmonary, renal, hepatic or neurologic dysfunction are not expected to survive one month.
  • Subjects receiving systemic immunosuppressive agents for the treatment of GVHD at the time of the CTL infusion will be excluded from receiving CTL, and subjects randomized to not receive CTL will also be removed from study if at the time of the CTL infusion they require systemic immunosuppression for treatment of GVHD
  • Donors must be negative for HIV-1, HIV-2, and HTLV-2, and have passed all screening tests for hepatitis.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00673868

Locations
United States, Pennsylvania
Penn State University
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Penn State University
Investigators
Principal Investigator: Kenneth G. Lucas, MD Penn State University
  More Information

No publications provided

Responsible Party: Kenneth G. Lucas, Penn State University
ClinicalTrials.gov Identifier: NCT00673868     History of Changes
Other Study ID Numbers: 26769
Study First Received: May 1, 2008
Last Updated: January 22, 2009
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 21, 2014