Allogeneic Multivirus - Directed Cytotoxic T Lymphocytes (CTL)

NCT01945814 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MUSTAT
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

EBV; CMV; Adenovirus

Outcome Measures

Primary Outcomes (1)

• Assessments of patients with adverse events after mukti-virus specific CTL infusion.

  The primary endpoint for this phase I trial are feasibility and safety. Safety of administration of CTLs is 45 days. The safety endpoint will be defined as acute GvHD grades III-IV within 45 days of the last dose of CTLs or grades 3-5 infusion-related adverse events within 45 days of the last CTL dose or grades 4-5 non-hematological adverse events within 45 days of the last CTL dose and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities.

  45 days

Secondary Outcomes (1)

• Assessments of viral load response to the CTL infusion

  3 months

Study Arms (2)

CTL for CMV seropositive donors

EXPERIMENTAL

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.

Drug: CTL for CMV seropositive donors

CTL for CMV naïve donors

EXPERIMENTAL

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.

Drug: CTL for CMV naïve donors

Interventions

CTL for CMV seropositive donors DRUG

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 dose is depending on the toxicity outcome, the maximum sample size for the this phase I portion of the trial is 14. Upon the completion of mCTL safety evaluation, additional 7 patients will be accrued at the MTD level to evaluate its antiviral activity.

CTL for CMV seropositive donors

CTL for CMV naïve donors DRUG

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 dose is depending on the toxicity outcome, the maximum sample size for the this phase I portion of the trial is 14. Upon the completion of mCTL safety evaluation, additional 7 patients will be accrued at the MTD level to evaluate its antiviral activity.

CTL for CMV naïve donors

Eligibility Criteria

• Age: 4 Weeks - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Received prior myeoloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or PBSC within 12 months
• Cells administered as;
• Prophylaxis for patients at risk of EBV, CMV, or Adenovirus.
• Treatment of reactivation or infection for EBV, CMV, or Adenovirus.
• Early treatment for single or multiple infections. Multiple infections with one reactivation and one controlled infection are eligible to enroll.
• Steroids less than 0.5 mg/kg/day prednisone
• Karnofsky/Lansky score of ≥ 50
• ANC greater than 500/µL.
• Bilirubin \<2x, AST \<3x, Serum creatinine \<2x upper limit of normal, Hgb \>8.0
• Pulse oximetry of \> 90% on room air
• Available multivirus-specific cytotoxic T lymphocytes
• Negative pregnancy test (if female of childbearing potential)
• Patient or parent/guardian capable of providing informed consent.

You may not qualify if:

• Patients with other uncontrolled infections (see 2.3.2 for definitions)
• Patients who received ATG, Campath, or other T cell immunosuppressive monoclonal antibodies in the last 28 days
• Received donor lymphocyte infusion in last 28 days
• Evidence of GVHD \> grade 2
• Active and uncontrolled relapse of malignancy
• Pregnant or lactating
• Unable to wean steroids to ≤0.5 mg/kg/day prednisone.
• Patients with Grade 3 hyperbilirubinemia

Sponsors & Collaborators

• Catherine Bollard: lead

Study Sites (1)

Childrens National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (1)

• Keller MD, Darko S, Lang H, Ransier A, Lazarski CA, Wang Y, Hanley PJ, Davila BJ, Heimall JR, Ambinder RF, Barrett AJ, Rooney CM, Heslop HE, Douek DC, Bollard CM. T-cell receptor sequencing demonstrates persistence of virus-specific T cells after antiviral immunotherapy. Br J Haematol. 2019 Oct;187(2):206-218. doi: 10.1111/bjh.16053. Epub 2019 Jun 20.

  PMID: 31219185 DERIVED

MeSH Terms

Conditions

Adenoviridae Infections

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Catherine Bollard, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director- Program for Cell Enhancement and Technologies for Immunotherapy (CETI)

Study Record Dates

• First Submitted: September 12, 2013
• First Posted: September 19, 2013
• Study Start: February 1, 2014
• Primary Completion: October 31, 2017
• Study Completion: October 16, 2018
• Last Updated: July 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)