CTL Therapy for Multivirus Infections

Overseen by Catherine Bollard, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Catherine Bollard

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Research Team

Catherine Bollard, MD

Principal Investigator

Children's National Research Institute

Eligibility Criteria

This trial is for patients with blood cancers or genetic diseases who've had a stem cell transplant within the last year. They should be at risk of, or currently fighting, CMV, EBV, or Adenovirus infections. Participants need to have stable vital signs and organ function and not be on high doses of steroids. Pregnant women and those with uncontrolled cancer relapse or other severe infections cannot join.

Inclusion Criteria

I am receiving early treatment for infections, including cases with both reactivation and controlled infections.

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

Available multivirus-specific cytotoxic T lymphocytes

Exclusion Criteria

I cannot reduce my steroid dose to less than or equal to 0.5 mg/kg/day.

I received a donor lymphocyte infusion in the last 28 days.

My cancer is currently growing or spreading.

Treatment Details

Interventions

• Allogeneic Multivirus-Directed CTL (Virus Therapy)

Trial Overview The study tests whether T cells (CTLs) grown from donors can prevent or treat viral infections like CMV, EBV, and Adenovirus in patients post-transplant. CTLs are trained in the lab to fight these viruses and then infused into patients to boost their immune response against potential life-threatening infections.

Participant Groups

Group I: CTL for CMV seropositive donors Experimental Treatment 1 Intervention

CTL for CMV seropositive donors - Allogeneic Multivirus - Directed Cytotoxic T lymphocytes (CTL) targeting CMV (IE1 and pp65), EBV (LMP2, EBNA1), and Adv (Hexon and Penton) for CMV seropositive donors- three different dose levels are selected, starting with 5 x 106 (a T cell number more than an order of magnitude lower than that administered at the time of an unmanipulated marrow infusion), followed by 1 x 107 and a final dose 2 x 107 mCTLs/m2. Two additional doses (at the same level)will be administered 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL.

Group II: CTL for CMV naïve donors Experimental Treatment 1 Intervention

CTL for CMV naïve donors - Allogeneic Multivirus - Directed Cytotoxic T lymphocytes (CTL) targeting CMV (IE1 and pp65), EBV (LMP2, EBNA1), and Adv (Hexon and Penton)for CMV naïve donors-each group will undergo an identical dose escalation. Three different dose levels are selected, starting with 5 x 106 (a T cell number more than an order of magnitude lower than that administered at the time of an unmanipulated marrow infusion), followed by 1 x 107 and a final dose 2 x 107 mCTLs/m2. Two additional doses (at the same level)will be administered 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL.

Who Is Running the Clinical Trial?

Catherine Bollard

Lead Sponsor

Trials

13

Recruited

290+