cmv ctls in neonates with cmv infection

Conditions: Congenital Cytomegaloviral (CMV) Disease

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

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.