Cytotoxic T Cells to Prevent Virus Infections

NCT01923766 | Completed Phase 1 DMC

• 1 other identifier: ACTCAT2
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

CMV; EBV; Adenovirus Infections

Keywords

Transplantation

Outcome Measures

Primary Outcomes (1)

• To assess the safety of administration of CTLs

  The primary endpoint is to assess the safety of administration of CTLs at 45 days post-infusion. The safety endpoint will be defined as acute GvHD grades III-IV or grade 3 or higher toxicity. Other toxicities to consider include GI , renal , hemorrhagic , cardiovascular, neurologic toxicity, coagulation, vascular and pulmonary toxicity. For the trial, two patients are allocated in each cohort and are followed for 45 days post IV injection of virus-specific T-cells for evaluation of DLTs. A maximum 18 patients will be accrued into each group. The final maximum tolerated dose (MTD) will be the dose with probability closest to the target toxicity rate at these termination points. The trial continues until a minimum of 12 patients have been treated. The trial will stop when the maximum 18 patients have been treated, or when six patients have been treated at the current MTD. We therefore expect to enroll between 12-18 patients into this trial.

  At 45 days post-infusion

Secondary Outcomes (1)

• Viral load

  Viral load will be monitored before infusion and after infusion weekly for a total of 60 days.

Study Arms (1)

Cytotoxic T lymphocytes (CTLs)

EXPERIMENTAL

Cytotoxic T lymphocytes (CTLs). CMV/AdV /EBV specific T cells will be given by slow intravenous injection over 1-2 minutes. Four dose levels will be explored. The lowest dose level will be 5x106cells/m2 and the highest will be 2.5x107/m2. During the dose escalation phase two to six patients will be entered at each dose level (depending on toxicity). If there are no toxicities and immunological efficacy is not seen at any dose, then the doses will be further escalated after additional local and federal approval.

Drug: Cytotoxic T lymphocytes (CTLs).

Interventions

Cytotoxic T lymphocytes (CTLs). DRUG

This Phase I dose-escalation trial is designed to evaluate the safety of donor-derived cytotoxic T lymphocytes (CTLs). Dose escalation is guided by the modified continual reassessment method (mCRM) in order to determine the maximum tolerated dose (MTD). For each group, MTD is defined as the dose at which the probability of DLT is at most 21%. Four dose levels are being evaluated namely, 5x106 cells/m2, 1.0x107 cells/m2, 1.5x107 cells/m2 and 2.5x107 cells/m2 with prior probabilities of toxicity estimated at 5%, 7.1%, 10% and 21%, respectively. Two patients are allocated in each cohort and are followed for 30 days post IV injection for evaluation of DLTs. The trial continues until a minimum of 12 patients have been treated and stop when the maximum 18 patients have been treated.

Cytotoxic T lymphocytes (CTLs)

Eligibility Criteria

• Age: 4 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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%

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Children's National Research Institute: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (2)

Childrens National Medical Center

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

Location

Amanda Olson, MD

Houston, Texas, United States

Location

MeSH Terms

Conditions

Adenoviridae Infections

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Catherine M Bollard, M.D

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director- Center for Emerging Technologies in Immune Cell Therapies (CETI)

Study Record Dates

• First Submitted: August 8, 2013
• First Posted: August 16, 2013
• Study Start: September 1, 2013
• Primary Completion: March 25, 2020
• Study Completion: March 25, 2020
• Last Updated: July 14, 2020

Record last verified: 2020-07

Locations

US (2)