CMV CTLs in Neonates With CMV Infection
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Biological: 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.
Other Names:
Drug: 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
Other Names:
|
| Experimental: Cohort 2 Antiviral medication + CMV CTLs Patients will receive both anti-viral medication and CMV CTLs |
Biological: 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.
Other Names:
Drug: 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
Other Names:
|
| Active Comparator: Cohort 2 Antiviral medication only Patients will only receive anti-viral therapy |
Drug: 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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- To determine the safety of giving CMV CTLs combined with anti-viral therapy in neonates with CMV [12 weeks]
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
- To determine response rates to treatment with CMV CTLS and anti-viral medication [12 weeks]
response rates will be measured by monitoring CMB PCR levels. A complete response to CMV-CTLs will be those with undetectable viral load by qRT-PCR
Eligibility Criteria
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
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Cortical or cerebral malformation
-
Chorioretinitis
-
Severe neonatal hearing loss
-
CMV DNA by PCR in CNS
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Increased WBC for age in CNS
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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
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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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington University | Saint Louis | Missouri | United States | 63130 |
| 2 | New York Medical College | Valhalla | New York | United States | 10595 |
| 3 | Nationwide Children's Hosptial | Columbus | Ohio | United States | 43205 |
| 4 | Children's Hospital of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- New York Medical College
Investigators
- Principal Investigator: Mitchell Cairo, MD, New York Medical College
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NYMC 597