Clinical trial NCT05564598: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Congenital Cytomegaloviral (CMV) Disease
Lead sponsor: New York Medical College
Sponsor class: OTHER
First posted: 2022-10-03
Enrollment: 23
Sex: ALL
Minimum age (years): 0
Maximum age (years): 21
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: To determine the safety of giving CMV CTLs combined with anti-viral therapy in neonates with CMV
timeFrame: 12 weeks
measure: To determine response rates to treatment with CMV CTLS and anti-viral medication
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Vallhala
country: United States
facility: New York Medical College
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hosptial
state: Ohio
Study officials:
affiliation: New York Medical College
name: Mitchell Cairo, MD
role: PRINCIPAL_INVESTIGATOR
References: