CMV CTLs in Neonates With CMV Infection

New York Medical College

Status and phase

Enrolling

Phase 2

Conditions

Congenital Cytomegaloviral (CMV) Disease

Treatments

Biological: CMV Cytotoxic T-Lymphocytes

Drug: Anti-viral Therapy

Study type

Interventional

Funder types

Other

Identifiers

NCT05564598

NYMC 597

1R01FD007837-01 (Other Grant/Funding Number)

Details and patient eligibility

About

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

Full 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

Enrollment

23 estimated patients

Sex

All

Ages

Under 21 days old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

23 participants in 3 patient groups

Cohort 1 Safety Run-in

Experimental group

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.

Treatment:

Drug: Anti-viral Therapy

Biological: CMV Cytotoxic T-Lymphocytes

Cohort 2 Antiviral medication + CMV CTLs

Experimental group

Description:

Patients will receive both anti-viral medication and CMV CTLs

Treatment:

Drug: Anti-viral Therapy

Biological: CMV Cytotoxic T-Lymphocytes

Cohort 2 Antiviral medication only

Active Comparator group