CTL Therapy for Multivirus Infections

No longer recruiting at 1 trial location

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Catherine Bollard

Must not be taking: ATG, Campath

Disqualifiers: Uncontrolled infections, GVHD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 45 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to prevent or treat viral infections in individuals who have received a stem cell transplant for blood-related conditions. The treatment uses special T cells, grown in a lab to recognize and combat viruses like cytomegalovirus (CMV), Epstein Barr Virus (EBV), and adenovirus (AdV). Known as Allogeneic Multivirus-Directed CTL therapy, this approach aims to determine if these cells can help prevent serious infections while the immune system recovers post-transplant. This trial may suit someone who has had a stem cell transplant and faces the risk of or is experiencing reactivation of these viruses. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you must be on a low dose of steroids (less than 0.5 mg/kg/day prednisone) to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using special immune cells from donors, called T cells, might be safe for individuals who have undergone stem cell transplants. Studies suggest that these donor T cells can be safely transferred to patients and may help strengthen their immune systems over time. This indicates that these T cells are unlikely to cause harmful side effects for most individuals.

Positive results have been observed when T cells from a donor's blood are grown in a lab and then administered to a patient after a transplant. These T cells can help fight viruses like CMV, EBV, and adenovirus, which pose risks to those with weakened immune systems.

Previous research has reported no major safety issues, indicating that the treatment is generally well-tolerated. However, as this is an early phase trial, safety continues to be closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard antiviral medications that often target a single virus, the allogeneic multivirus-directed cytotoxic T lymphocytes (CTL) therapy is unique because it targets multiple viruses simultaneously, specifically CMV, EBV, and Adv. This approach is especially promising as it harnesses the body's immune cells, T lymphocytes, to attack these viruses in a targeted manner. Researchers are excited about this treatment because it offers a more comprehensive defense against viral infections, particularly for those with compromised immune systems, potentially leading to more effective and long-lasting protection than traditional antiviral drugs.

What evidence suggests that this trial's treatments could be effective for multivirus infections?

Research has shown that certain T cells, called CTLs, can help fight viral infections like CMV, EBV, and adenovirus, especially in patients with weakened immune systems after transplants. This trial will administer Allogeneic Multivirus-Directed CTLs, with separate treatment arms for CMV seropositive and CMV naïve donors. In some studies, patients who received these CTLs regained their ability to fight off CMV and EBV. These special T cells are grown in a lab to target and eliminate these viruses effectively. Even with donors who haven't had CMV, CTLs can still be developed to combat these viruses. Overall, CTLs offer hope for better control of these serious infections in vulnerable patients. ^{1 6 7 8 9}

Who Is on the Research Team?

Catherine Bollard, MD

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

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

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

Available multivirus-specific cytotoxic T lymphocytes

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

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multivirus-directed cytotoxic T lymphocytes (CTL) infusions targeting CMV, EBV, and adenovirus

45 days

3 visits (in-person) for dose administration

Follow-up

Participants are monitored for safety and effectiveness after CTL infusion

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Multivirus-Directed CTL

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01945814?cond=cytotoxic%20T%20lymphocytes&aggFilters=status:not%20rec%20enr%20act%20ter%20com,studyType:int&viewType=Table&rank=3

Allogeneic Multivirus - Directed Cytotoxic T Lymphocytes ... They observed recovery of immunity to CMV and EBV in all patients but an increase in adenovirus-specific T cells was only seen in patients who had evidence of ...

2. nature.com nature.com/articles/s41467-024-54595-2

Compassionate access to virus-specific T cells for adoptive ... Representative data from one of the multi-virus-specific T cell products with reactivity against AdV, BKV/JCV, CMV and EBV are shown in Fig. 5A.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3692015/

Expansion of T cells targeting multiple antigens of ... CTL that target at least two antigens each of CMV, EBV and Ad should have clinical benefit with broad coverage of all three viruses and enhanced control of CMV ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01570283

Study Details | NCT01570283 | ARMS - Rapidly Generated ... Cohort 1 treatment: Participants were administrated 5*10^6 mCTLs/m multivirusspecific T cells intravenously for treatment of EBV, CMV, Adenovirus, HHV6 and BK ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725013831

Long-Term Efficacy of Epstein-Barr Virus-Specific T Cells ... Our findings support the long-term efficacy of cellular immunotherapy in managing viral complications post-transplantation. Section snippets.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11113937/

The immune response to cytomegalovirus in allogeneic ... In this review, essential aspects in the immune recovery against CMV are discussed to improve the better understanding of the immune system relying on CMV ...

7. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT01945814/

Trial | NCT01945814 CTL for CMV naïve donors - Allogeneic Multivirus - Directed Cytotoxic T lymphocytes (CTL) targeting CMV (IE1 and pp65), EBV (LMP2, EBNA1), and Adv (Hexon and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7593558/

Harnessing T Cells to Control Infections After Allogeneic ... This review provides a brief overview of current cellular therapeutic strategies to prevent or treat pathogen-related complications after HSCT, ...

9. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT01945814?keyword=%22CMV%22

Allogeneic Multivirus - Directed Cytotoxic T Lymphocytes ... Therefore, these results suggest that transfer of naïve T cell (CB)-derived virus specific T cells to patients after CBT may be safe and facilitate long ...