CMV CTLs in Neonates With CMV Infection

NCT ID: NCT05564598

Last Updated: 2025-05-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-01
• Study Completion Date: 2028-10-31

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.

Funding source: FDA OOPD

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

Conditions

Congenital Cytomegaloviral (CMV) Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 Safety Run-in

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.

Group Type: EXPERIMENTAL

CMV Cytotoxic T-Lymphocytes

Intervention Type: BIOLOGICAL

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.

Anti-viral Therapy

Intervention Type: DRUG

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

Cohort 2 Antiviral medication + CMV CTLs

Patients will receive both anti-viral medication and CMV CTLs

Group Type: EXPERIMENTAL

CMV Cytotoxic T-Lymphocytes

Intervention Type: BIOLOGICAL

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.

Anti-viral Therapy

Intervention Type: DRUG

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

Cohort 2 Antiviral medication only

Patients will only receive anti-viral therapy

Group Type: ACTIVE_COMPARATOR

Anti-viral Therapy

Intervention Type: DRUG

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

Interventions

CMV Cytotoxic T-Lymphocytes

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: BIOLOGICAL

Anti-viral Therapy

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

Intervention Type: DRUG

Other Intervention Names

CTLs; valganciclovir, ganciclovir

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.

• Minimum Eligible Age: 0 Days
• Maximum Eligible Age: 21 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York Medical College

OTHER

Sponsor Role: lead

Responsible Party

Mitchell Cairo

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mitchell Cairo, MD

Role: PRINCIPAL_INVESTIGATOR

New York Medical College

Locations

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status: RECRUITING

Washington University

St Louis, Missouri, United States

Site Status: RECRUITING

New York Medical College

Vallhala, New York, United States

Site Status: RECRUITING

Nationwide Children's Hosptial

Columbus, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mitchell Cairo, MD

Role: CONTACT

mitchell_cairo@nymc.edu

914-594-2150

Edo Schaefer, MD

Role: CONTACT

eshaefe@nymc.edu

Facility Contacts

Neena Kapoor, MD

Role: primary

nkapoor@chla.usc.edu

Phillippe Friedlich, MD

Role: backup

pfriedlich@chla.usc.edu

Carol Kao, MD

Role: primary

kaoc@wustl.edu

Mitchell Cairo, MD

Role: primary

mitchell_cairo@nymc.edu

914-594-3650

Lauren Harrison, MSN

Role: backup

lauren_harrison@nymc.edu

617-285-7844

Masako Shimamura, MD

Role: primary

masako.shimamura@nationwidechildrens.org

Other Identifiers

1R01FD007837-01

Identifier Type: FDA

Identifier Source: secondary_id

View Link

NYMC 597

Identifier Type: -

Identifier Source: org_study_id