search
Back to results

CMV CTLs in Neonates With CMV Infection

Primary Purpose

Congenital Cytomegaloviral (CMV) Disease

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CMV Cytotoxic T-Lymphocytes
Anti-viral Therapy
Sponsored by
New York Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congenital Cytomegaloviral (CMV) Disease

Eligibility Criteria

0 Days - 21 Days (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age: ≤ 21 days of life
  • Birth Weight: ≥ 2500 gms
  • Gestational age: ≥ 34 weeks of age
  • Diagnosis of CMV viremia, viruria, and/or infection:Either one or more:

Elevated CMV by RT-PCR in urine, saliva, CSF, or plasma; and/or Positive urine culture for CMV

- Moderate or Severe CMV Disease

Any one or more of the following attributable to congenital CMV infection:

  • Thrombocytopenia (≤ 50,000 mm3)
  • Multiple petechiae
  • Hepatomegaly
  • Splenomegaly
  • Intrauterine growth retardation
  • Increased transaminases
  • Increased bilirubin
  • Microcephaly
  • Ventriculomegaly
  • Intracerebral calcifications
  • Periventricular echogenicity
  • Cortical or cerebral malformation
  • Chorioretinitis
  • Severe neonatal hearing loss
  • CMV DNA by PCR in CNS

  • Increased WBC for age in CNS

    • Minimal Organ Criteria Hematological: ANC ≥ 750/mm3, HgB ≥ 8gm/dl, Platelets ≥ 20,000/kmm3 Renal: Serum creatinine ≤ 1.0 mg/dl Hepatic: ALT/SGOT ≤3x upper normal limits
    • Donor Availability: Maternal donor available with a T-cell response CMV MACS® PepTivators. the donor is considered suitable if the percentage of IFN-gamma+ T cells is > 0.01% after stimulation with PepTivators.

Exclusion Criteria -

  • Patient receiving steroids (> 0.5 mg/kg prednisone equivalent) on the same day of CMV CTL infusion. Antenatal steroids for lung maturation will have been cleared prior to CMV diagnosis.
  • Concomitant enrollment in another experimental clinical trial investigating the treatment of neonatal CMV viremia and/or infection.
  • Any medical condition that could compromise participation in the study according to the investigator's assessment.
  • Known history of HIV infection in the mother.
  • Patient's legally authorized representative unwilling or unable to comply with the protocol or unable to give informed consent.

Sites / Locations

  • Washington University
  • New York Medical CollegeRecruiting
  • Nationwide Children's Hosptial
  • Children's Hospital of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Cohort 1 Safety Run-in

Cohort 2 Antiviral medication + CMV CTLs

Cohort 2 Antiviral medication only

Arm Description

The first 3 patients enrolled will receive both anti-viral medication and CMV CTLs, and treatment will be staggered every 28 days from the last dose of CMV CTLs from the prior patient.

Patients will receive both anti-viral medication and CMV CTLs

Patients will only receive anti-viral therapy

Outcomes

Primary Outcome Measures

To determine the safety of giving CMV CTLs combined with anti-viral therapy in neonates with CMV
the incidence and severity of Grade I-IV acute GVHD within 8 weeks that is probably or directly related to CMV-CTL infusion after last CMV CTL infusion will be evaluated to determine the safety profile of CMV CTLs in neonates
To determine response rates to treatment with CMV CTLS and anti-viral medication
response rates will be measured by monitoring CMV PCR levels. A complete response to CMV-CTLs will be those with undetectable viral load by qRT-PCR

Secondary Outcome Measures

Full Information

First Posted
September 26, 2022
Last Updated
September 12, 2023
Sponsor
New York Medical College
search

1. Study Identification

Unique Protocol Identification Number
NCT05564598
Brief Title
CMV CTLs in Neonates With CMV Infection
Official Title
A Phase II Open-Label Randomized Study of Anti-Viral Antibiotic Therapy With and Without Familial (Maternal) Cytomegalovirus (CMV) Cytotoxic T Lymphocytes (CTLs) in Neonates With Moderate/Severe Maternal Acquired CMV Infection
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2023 (Actual)
Primary Completion Date
October 31, 2027 (Anticipated)
Study Completion Date
October 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York Medical College

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Patients with moderate or severe CMV disease less than 21 days old who have a maternal donor who has a CMV response to the peptivators will be screened. All patients will receive treatment with valganciclovir or ganciclovir. There is a safety run in with treatment with CMV CTLs in cohort 1 and if found to be safe, will proceed to cohort 2 for randomization to receive antiviral therapy with or without CMV CTLs.
Detailed Description
Given the vulnerability and poor outcomes of preterm neonates and neonates in general to viral infection, including the need for prolonged antiviral therapy for 6 or more months to achieve just modest improvements in sensorineural functions, CMV CTL therapy offers a promising alternative. CMV CTL treatment will build on the hosts innate immune capacity to create a more effective and permanent defense against collateral injury arising from CMV infections. Patients who meet all inclusion/exclusion criteria with a maternal donor who meet all donor criteria will be enrolled onto study. Cohort 1 is a safety run-in; the first 3 patients enrolled will be treated with anti-viral and CMV CTLs. The external DSMB will review the data from the first patient, and if there are no adverse events or dose-limiting toxicities observed, approve patient 2, and then 3, 28 days after the prior patients last CTL infusion. Assuming there are no adverse events in any of the first 3 patients, the study will proceed to Cohort 2. Cohort 2 will be randomized 1:1 to either anti-viral treatment alone or anti-viral treatment plus CMV CTLs. Patients who are randomized to receive CMV CTLs will get their first infusion on Day 0. If the patient fails to achieve a CR, they may receive one infusion every 2 weeks up to 5 maximum CMV CTL infusions as long as there are no DLTs or AEs observed

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Cytomegaloviral (CMV) Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
23 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 Safety Run-in
Arm Type
Experimental
Arm Description
The first 3 patients enrolled will receive both anti-viral medication and CMV CTLs, and treatment will be staggered every 28 days from the last dose of CMV CTLs from the prior patient.
Arm Title
Cohort 2 Antiviral medication + CMV CTLs
Arm Type
Experimental
Arm Description
Patients will receive both anti-viral medication and CMV CTLs
Arm Title
Cohort 2 Antiviral medication only
Arm Type
Active Comparator
Arm Description
Patients will only receive anti-viral therapy
Intervention Type
Biological
Intervention Name(s)
CMV Cytotoxic T-Lymphocytes
Other Intervention Name(s)
CTLs
Intervention Description
Patients will receive maternal CMV CTLs on day 0. Additional doses of CMV CTLs may be re-infused at a minimum of every two weeks for a maximum of five total infusions (maximum 2.5 x 104 CD3/kg) only in patients not achieving a CR and no prior dose limiting toxicity of any prior dose.
Intervention Type
Drug
Intervention Name(s)
Anti-viral Therapy
Other Intervention Name(s)
valganciclovir, ganciclovir
Intervention Description
All patients will receive anti-viral therapy with one of the following: 4.2.2 Valganciclovir Dosing: 16 mg/kg/dose PO q12h OR 4.2.3 Ganciclovir Dosing: 6 mg/kg/dose IV q12h Dose adjustments: Reduce dose by 50% for ANC less than 500 cells/mm3 Hold the dose if ≤ 200 cells/mm3 until recovery ≥ 500 cells/mm3 Treatment will continue for 6 months
Primary Outcome Measure Information:
Title
To determine the safety of giving CMV CTLs combined with anti-viral therapy in neonates with CMV
Description
the incidence and severity of Grade I-IV acute GVHD within 8 weeks that is probably or directly related to CMV-CTL infusion after last CMV CTL infusion will be evaluated to determine the safety profile of CMV CTLs in neonates
Time Frame
12 weeks
Title
To determine response rates to treatment with CMV CTLS and anti-viral medication
Description
response rates will be measured by monitoring CMV PCR levels. A complete response to CMV-CTLs will be those with undetectable viral load by qRT-PCR
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Days
Maximum Age & Unit of Time
21 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age: ≤ 21 days of life Birth Weight: ≥ 2500 gms Gestational age: ≥ 34 weeks of age Diagnosis of CMV viremia, viruria, and/or infection:Either one or more: Elevated CMV by RT-PCR in urine, saliva, CSF, or plasma; and/or Positive urine culture for CMV - Moderate or Severe CMV Disease Any one or more of the following attributable to congenital CMV infection: Thrombocytopenia (≤ 50,000 mm3) Multiple petechiae Hepatomegaly Splenomegaly Intrauterine growth retardation Increased transaminases Increased bilirubin Microcephaly Ventriculomegaly Intracerebral calcifications Periventricular echogenicity Cortical or cerebral malformation Chorioretinitis Severe neonatal hearing loss CMV DNA by PCR in CNS Increased WBC for age in CNS Minimal Organ Criteria Hematological: ANC ≥ 750/mm3, HgB ≥ 8gm/dl, Platelets ≥ 20,000/kmm3 Renal: Serum creatinine ≤ 1.0 mg/dl Hepatic: ALT/SGOT ≤3x upper normal limits Donor Availability: Maternal donor available with a T-cell response CMV MACS® PepTivators. the donor is considered suitable if the percentage of IFN-gamma+ T cells is > 0.01% after stimulation with PepTivators. Exclusion Criteria - Patient receiving steroids (> 0.5 mg/kg prednisone equivalent) on the same day of CMV CTL infusion. Antenatal steroids for lung maturation will have been cleared prior to CMV diagnosis. Concomitant enrollment in another experimental clinical trial investigating the treatment of neonatal CMV viremia and/or infection. Any medical condition that could compromise participation in the study according to the investigator's assessment. Known history of HIV infection in the mother. Patient's legally authorized representative unwilling or unable to comply with the protocol or unable to give informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mitchell Cairo, MD
Phone
914-594-2150
Email
mitchell_cairo@nymc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Edo Schaefer, MD
Email
eshaefe@nymc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mitchell Cairo, MD
Organizational Affiliation
New York Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carol Kao, MD
Email
kaoc@wustl.edu
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mitchell Cairo, MD
Phone
914-594-3650
Email
mitchell_cairo@nymc.edu
First Name & Middle Initial & Last Name & Degree
Lauren Harrison, MSN
Phone
617-285-7844
Email
lauren_harrison@nymc.edu
Facility Name
Nationwide Children's Hosptial
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Masako Shimamura, MD
Email
masako.shimamura@nationwidechildrens.org
Facility Name
Children's Hospital of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Bunin, MD
Phone
215-590-2255
Email
buninn@email.chop.edu

12. IPD Sharing Statement

Learn more about this trial

CMV CTLs in Neonates With CMV Infection

We'll reach out to this number within 24 hrs