Cytotoxic T Cells to Prevent Virus Infections

• Status: Completed
• Trial end date: 2020-03-25
• Target enrollment: 0
• Participant gender: All

Summary

In this study, investigators are trying to see if infusion of "m-CTLs" will prevent or treat cytomegalovirus (CMV), Epstein Barr Virus (EBV) and adenovirus (AdV) reactivation or infection after cord blood transplant.

Patients with blood cell cancer, other blood disease or a genetic disease may receive a cord blood transplant (UCBT) from an unrelated donor. After receiving a cord blood transplant, they are at risk of infections until a new immune system to fight infections grows from the cord blood cells. In this study, investigators are trying to give special cells from the cord blood called T cells. These cells will try to fight viruses that can cause infection.

Investigators will test to see if blood cells from donor that have been grown in a special way, can prevent patients from getting an infection. EBV, AdV and CMV are viruses that can cause serious life-threatening infections in patients who have weak immune systems after transplant.

T lymphocytes can kill viral cells but normally there are not enough of them to kill all the virus infected cells after transplant. Some researcher have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person during a viral infection after a bone marrow transplant. Some of these studies have shown a positive therapeutic effect in patients receiving the CTLs (specially trained T cells) after a viral infection in the post-transplant period. In this study we are trying to prevent or treat viral infections by given the CTLs soon after getting the umbilical cord blood transplant.

With this study, investigators want to see if they can use a kind of white blood cell called T cells to prevent or treat AdV, EBV and CMV infection. Investigators will grow these T cells from the cord blood before transplant. These cells have been trained to attack adenovirus/EBV/CMV- infected cells and are called multivirus-specific cytotoxic (killer) T-cells or "m-CTL." Investigators would plan to give patients one dose of m-CTL any time from 30 to 364 days after your transplant. They have used T cells made in this way from the blood of donors to prevent infections in patients who are getting a bone marrow or blood stem cell transplant but this will be the first time investigators make them from cord blood.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's National Research Institute; Children's Research Institute
• Collaborator: M.D. Anderson Cancer Center

Criteria

Inclusion criteria at the time of Procurement:

• Patient with malignant or nonmalignant diseases who are candidates for transplant.

• Patients must have a CB unit (or units) matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens.

Inclusion criteria at the time of CTL infusion:

• 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.

• Lansky/Karnofsky scores >60

• Absolute neutrophil count (ANC) greater than 500/ul.

• No evidence of GVHD > Grade II at time of enrollment.

• Life expectancy > 30 days

• Absence of severe renal disease (Creatinine > x 3 normal for age)

• Absence of severe hepatic disease. Direct bilirubin must be < 3 mg/dl and AST < 5x upper limit of normal.

• Patient must be at least 30 days post transplant to be eligible to receive CTL

• Written informed consent and/or signed assent line from patient, parent or guardian.

• Patient not on Fi02 of >60%

Exclusion criteria at the time of Procurement

• Pregnant or lactating

• Patients with active central nervous system disease

• Patients with Karnofsky performance status <70%

• Patients with grade 3 or 4 or primary myelofibrosis

• Patients with suitable related donors

Exclusion criteria at the time of CTL infusion

• Pregnant or lactating

• Unable to wean steroids to ≤0.5 mg/kg/day prednisone.

• 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.