Allogeneic Multivirus - Directed Cytotoxic T Lymphocytes (CTL)

• Status: Active, not recruiting
• Trial end date: 2022-09-01
• Target enrollment: 0
• Participant gender: All

Summary

In this study, investigators are trying to see if infusion of T cells (called CTLs) will prevent or treat cytomegalovirus (CMV), Epstein Barr Virus (EBV) and adenovirus (AdV) reactivation or infection.

Patients with blood cell cancer, other blood disease or a genetic disease may receive a stem cell transplant. After receiving 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 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 after a viral infection in the post-transplant period.

Investigators will grow these cells from donor in the laboratory in a way that will train them to recognize and remove viruses when the T cells are given after a transplant. Since most donors have previously been infected with EBV, CMV, and adenovirus, investigators are able to use their T cells that remember these viruses to grow the CTLs. However, they now also have a new way of growing CTLs from donors who have not been infected with CMV.

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

Details

• Lead Sponsor: Catherine Bollard

Criteria

Inclusion Criteria:

• Recipient Inclusion Criteria at the time of CTL infusion

1. Received prior myeoloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or PBSC within 12 months

2. Cells administered as;

1. Prophylaxis for patients at risk of EBV, CMV, or Adenovirus.

2. Treatment of reactivation or infection for EBV, CMV, or Adenovirus.

3. Early treatment for single or multiple infections. Multiple infections with one reactivation and one controlled infection are eligible to enroll.

3. Steroids less than 0.5 mg/kg/day prednisone

4. Karnofsky/Lansky score of ≥ 50

5. ANC greater than 500/µL.

6. Bilirubin <2x, AST <3x, Serum creatinine <2x upper limit of normal, Hgb >8.0

7. Pulse oximetry of > 90% on room air

8. Available multivirus-specific cytotoxic T lymphocytes

9. Negative pregnancy test (if female of childbearing potential)

10. Patient or parent/guardian capable of providing informed consent.

Exclusion Criteria:

• Recipient Exclusion criteria at the time of CTL infusion

1. Patients with other uncontrolled infections (see 2.3.2 for definitions)

2. Patients who received ATG, Campath, or other T cell immunosuppressive monoclonal antibodies in the last 28 days

3. Received donor lymphocyte infusion in last 28 days

4. Evidence of GVHD > grade 2

5. Active and uncontrolled relapse of malignancy

6. Pregnant or lactating

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

8. Patients with Grade 3 hyperbilirubinemia