Congenital Cytomegaloviral (CMV) DiseasePhase 2NCT05564598
CMV CTLs in Neonates With CMV Infection
A Phase 2 study testing CMV Cytotoxic T-Lymphocytes and Anti-viral Therapy in people with Congenital Cytomegaloviral (CMV) Disease, run by New York Medical College at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 21 days
- Conditions the study is for
- Congenital Cytomegaloviral (CMV) Disease
- What is being tested?
- CMV Cytotoxic T-Lymphocytes and Anti-viral Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Jul 2023to 31 Oct 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 21 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Show all 25Show fewer
- 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.
Who cannot join
- 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 locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Edo Schaefer, MD contact
United States4 sites, 4 recruiting
- Recruiting
Nationwide Children's Hosptial
Columbus, Ohio, 43205
Masako Shimamura, MD, masako.shimamura@nationwidechildrens.org
- Recruiting
Children's Hospital Los Angeles
Los Angeles, California, 90027
Neena Kapoor, MD, nkapoor@chla.usc.edu
Phillippe Friedlich, MD, pfriedlich@chla.usc.edu
- Recruiting
Washington University
St Louis, Missouri, 63130
Carol Kao, MD, kaoc@wustl.edu
- Recruiting
New York Medical College
Valhalla, New York, 10595
Mitchell Cairo, MD, 914-594-3650, mitchell_cairo@nymc.edu
Lauren Harrison, MSN, 617-285-7844, lauren_harrison@nymc.edu
About this study
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
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
Read the 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
- Being tested
- CMV Cytotoxic T-Lymphocytes, Anti-viral Therapy
- Medical subject headings
- Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV Cytotoxic T-LymphocytesBiological
Also called CTLs
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 TherapyDrug
Also called valganciclovir, ganciclovir
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
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Safety Run-in | Experimental | 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. Receives: Biological: CMV Cytotoxic T-Lymphocytes; Drug: Anti-viral Therapy |
| Cohort 2 Antiviral medication + CMV CTLs | Experimental | Patients will receive both anti-viral medication and CMV CTLs Receives: Biological: CMV Cytotoxic T-Lymphocytes; Drug: Anti-viral Therapy |
| Cohort 2 Antiviral medication only | Active comparator | Patients will only receive anti-viral therapy Receives: Drug: Anti-viral Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 weeks
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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2022
- Study start1 Jul 2023
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Cytomegaloviral (CMV) DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York Medical College
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mitchell Cairo, New York Medical College
- Investigators
- Mitchell Cairo, MD, Principal investigator, New York Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05564598
- Sponsor's protocol ID
- NYMC 597
- Other IDs
- 1R01FD007837-01
- Status last verified
- Mar 2026
- First submitted
- 26 Sep 2022
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No