Recruitment

Recruitment Status
Completed
Estimated Enrollment
18

Inclusion Criterias

Absolute neutrophil count (ANC) greater than 500/ul.
Recipients of at least one unmanipulated cord blood unit fractionated into 2 fractions (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral disease or reactivation.
Absence of severe hepatic disease. Direct bilirubin must be < 3 mg/dl and AST < 5x upper limit of normal.
...
Absolute neutrophil count (ANC) greater than 500/ul.
Recipients of at least one unmanipulated cord blood unit fractionated into 2 fractions (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral disease or reactivation.
Absence of severe hepatic disease. Direct bilirubin must be < 3 mg/dl and AST < 5x upper limit of normal.
Life expectancy > 30 days
No evidence of GVHD > Grade II at time of enrollment.
Patient must be at least 30 days post transplant to be eligible to receive CTL
Lansky/Karnofsky scores >60
Patient not on Fi02 of >60%
Absence of severe renal disease (Creatinine > x 3 normal for age)
Written informed consent and/or signed assent line from patient, parent or guardian.

Exclusion Criterias

Unable to wean steroids to ≤0.5 mg/kg/day prednisone.
Pregnant or lactating
Patients with other uncontrolled infections (except CMV and/or adenovirus and/or EBVemia).
...
Unable to wean steroids to ≤0.5 mg/kg/day prednisone.
Pregnant or lactating
Patients with other uncontrolled infections (except CMV and/or adenovirus and/or EBVemia).
Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease.

Summary

Conditions
  • Adenovirus Infections
  • CMV
  • EBV
Type
Interventional
Phase
Phase 1
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Younger than 125 years
Gender
Both males and females

Description

Umbilical cord blood (UCB) is a readily available alternative source of Hemotopoietic Stem Cells (HSCs) that is capable of reconstituting hematopoiesis after myeloablative therapy. More than 280,000 UCB units have been banked world-wide and more than 13,000 unrelated donor UCB transplantations have ...

Umbilical cord blood (UCB) is a readily available alternative source of Hemotopoietic Stem Cells (HSCs) that is capable of reconstituting hematopoiesis after myeloablative therapy. More than 280,000 UCB units have been banked world-wide and more than 13,000 unrelated donor UCB transplantations have been performed. UCB transplants offer several advantages over adult bone marrow or peripheral blood stem cell transplants, including: 1) rapid availability, 2) absence of donor risk, 3) low risk of transmissible infectious diseases, 4) low risk of acute Graft versus Host Disease (GvHD) in the setting of Human Leukocye Antigen (HLA) mismatch (as compared to recipients of unrelated donor marrow and peripheral blood). UCB is particularly beneficial for patients of ethnic and racial minority descent for whom adult marrow and blood donors often cannot be identified. In a larger series the neutrophil engraftment has been reported as high as 92%. The incidence of acute GvHD reported in larger series ranges from 33-44% to 11-22% for grades II-IV and III-IV acute GvHD, respectively. The incidence of chronic GvHD ranges from 0-25%. These results are particularly notable since most UCB donor-recipient pairs are 1-2 HLA antigen mismatched. However, infection related TRMs are still of concern after UCBT. The rate of hemopoietic recovery is slower after UCBT; therefore infectious complications including viral infections occur frequently. Multi virus Specific T cells from Cord Blood could be applied with comparable success to recipients of CB transplants; however, certain obstacles to the extension of this approach must be circumvented. These include: (i) the limited numbers of CB T-cells available for manipulation and (ii) the naivety of CB T-cells. Hence, the development of virus-protective T-cell therapy for patients undergoing CBT requires the priming and extensive expansion of naïve T-cells rather than the more limited and simple direct expansion of pre-existing virus-specific memory T-cell populations from virus-experienced donors. Further, CB T-cells have lower cytotoxic activity and higher activation-induced cell death than peripheral blood T-cells. These limitations have prevented the production of virus-specific cord blood-derived CTL in sufficient numbers for clinical use. Because of these challenges, only a few reports document the generation of antigen-specific T cells from CB. Sun et al first reported the ability to generate EBV-specific CD4+ T cells using EBV-transformed B-cells, or lymphoblastoid cell lines (LCL). Park et al then reported the ability to generate CMV-pp65-specific T cells from cord blood by using CMV-immune complex-loaded DCs, CMV lysate, and IL-12 and IL-7. The study at Baylor College of Medicine (BCM)showed that Ad5f35pp65-transduced CB-derived APC could be used to generate large numbers of autologous T-cells specific for both CMV and Ad, even from the phenotypically naive T-cell subpopulation. Addition of EBV-transformed B-lymphoblastoid cell lines (LCL) to the APCs allowed the Ad/CMV specificity of the CB T-cells to be extended to EBV. In addition, the multivirus-specific T-cells recognized an array of epitopes after only 2 weeks expansion in vivo. We therefore suggest that our ability to generate virus-specific CTL from CB against a plethora of epitopes recognized by both CD4+ and CD8+ T-cells should minimize the risk of viral escape and maximize therapeutic benefit on administration of these cells to cord blood recipients at risk of severe viral disease. A clinical trial using CB-derived multi-virus specific T cells for the prevention and treatment of viral infection after CBT was started at BCM. (Clinical Trial #: NCT01017705).

Inclusion Criterias

Absolute neutrophil count (ANC) greater than 500/ul.
Recipients of at least one unmanipulated cord blood unit fractionated into 2 fractions (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral disease or reactivation.
Absence of severe hepatic disease. Direct bilirubin must be < 3 mg/dl and AST < 5x upper limit of normal.
...
Absolute neutrophil count (ANC) greater than 500/ul.
Recipients of at least one unmanipulated cord blood unit fractionated into 2 fractions (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral disease or reactivation.
Absence of severe hepatic disease. Direct bilirubin must be < 3 mg/dl and AST < 5x upper limit of normal.
Life expectancy > 30 days
No evidence of GVHD > Grade II at time of enrollment.
Patient must be at least 30 days post transplant to be eligible to receive CTL
Lansky/Karnofsky scores >60
Patient not on Fi02 of >60%
Absence of severe renal disease (Creatinine > x 3 normal for age)
Written informed consent and/or signed assent line from patient, parent or guardian.

Exclusion Criterias

Unable to wean steroids to ≤0.5 mg/kg/day prednisone.
Pregnant or lactating
Patients with other uncontrolled infections (except CMV and/or adenovirus and/or EBVemia).
...
Unable to wean steroids to ≤0.5 mg/kg/day prednisone.
Pregnant or lactating
Patients with other uncontrolled infections (except CMV and/or adenovirus and/or EBVemia).
Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease.

Locations

Houston, Texas
Washington, District of Columbia, 20010
Houston, Texas
Washington, District of Columbia, 20010

Tracking Information

NCT #
NCT01923766
Collaborators
M.D. Anderson Cancer Center
Investigators
  • Principal Investigator: Catherine M Bollard, M.D Children's National Research Institute
  • Catherine M Bollard, M.D Children's National Research Institute