Profylakse av cytomegalovirusinfeksjon med adoptiv celle-inmunoterapi (INMUNOCELL)
Anti-CMV pilot klinisk studie: profylakse av cytomegalovirusinfeksjon i haploidentisk transplatasjon av hematopoetiske stamceller med adoptiv celle immunterapi
Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality for recipients of allogeneic hematopoietic stem cell transplantation(HSCT). Recently, strategies based on immunotherapy adoptive cells (IAC) with anti-CMV Cytolitic T Lymphocytes (CMV-CTLs) has been incorporated to prevent or treat CMV after HSCT. The aim to study donor derived CMV-CTLs after haploidentical HSCT (HAPLO) as prophylaxis for CMV infection in transplant patients. CMV-CTLs will be administer at day 21 (+-7 days) post-HAPLO. CMV DNA levels with quantitative PCR will be weekly monitored.
Studieoversikt
Detaljert beskrivelse
In HAPLO, CMV infection and disease are more frequent than in other type of HSCT, this is related to delayed immune reconstitution after transplant increasing post-transplant infectious complications. Approximately 60% of patients reactivated CMV infection after HAPLO and 15%, developed CMV disease afecting organs and causing the death of the patient in 8% of CMV disease cases.
If patient and donor are eligible, it will take 1x10^9 cells from donor leukapheresis. Donor cells will be selected and procesed by CliniMACs PRODIGY and after 12h it will obtain 7mL of CMV-CTLs. It will use 6mL of CMV-CTLs to infused a dose of 1x10^5 cells/kg in our patient. The donor derived CMV-CTL cells will be transfused into the patients' intravenous line. The patients will receive the dose of CMV-CTL cells when they are sero-positive for CMV-DNA 21 (+- 7 days) days after transplant.
The CMV-DNA levels will be monitored weekly for at least 100 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then the patient will receive treatment with anti-CMV comercial drugs.
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiekontakt
- Navn: Miriam Sanchez-Escamilla, MD
- Telefonnummer: +34646393234
- E-post: msanchez@idival.org
Studer Kontakt Backup
- Navn: Lucía Lavín Alconero, Phd
- E-post: eclinicos5@idival.org
Studiesteder
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Santander, Spania
- Rekruttering
- Hospital Marques de Valdecilla
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Ta kontakt med:
- enrique ocio
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
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Adult patients who received an alogeneic stem cell transplantation from haploidentical donors (HAPLO).
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Any source of stem cells (peripheral blood or bone marrow).
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CMV-seropositive donors.
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Negative pregnancy test in women.
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Signed writen informed consent.
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DONORS:
- HLA haploidentical and CMV-seropositve donors.
- Donor must be checked and suitable.
- Signed writen informed consent.
- Donor without active infection evidence at leukapheresis.
Exclusion Criteria:
- Patients without haploidentical CMV-seropositive donors.
- Patients who are not suitable for follow up visits.
CMV-CTLs Infusion Criteria:
- Hematopoiesis recovery at least partial (neutrophil counts >0.5x10^9/L in at least 3 consecutive samples post-transplant).
CMV-CTLs NON-Infusion Criteria:
- Patients receiving corticosteroid (dose of 0.5mg/kg/day of prednisone or equivalent) at infusion.
- ECOG > or = 3.
- Organic toxicities grade > or = 3.
- Patients who received ATG, donor lymphocytes or alemtuzuamb, 28 days pre-infusion.
- Patients with uncontroled infection defined by fevers and/or inestability and/or infection not resolved.
- Persistent fevers 3 days before infusion.
- Acute Graft Versus Host Disease (GVHD) grade II-IV.
- Relapse or progression after transplant and before infusion day.
- CMV reactivation/infection after transplant and before infusion day.
Patients who don´t fill infusion criteria, after day 28 post-HAPLO, will be considered screening failures and will be out of the study.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: CMV CTLs
1x10^5 CMV-CTLs/kg |
The donor derived cytomegalovirus specific T lymphocytes (CMV-CTL) will be transfused to the patients. The patients will receive CMV-CTL cells when their donors are sero-positive for CMV-DNA 21 days after transplant. The CMV-DNA levels will be monitored weekly for at least 100 days after the HAPLO. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive a CMV specific antiviral drug. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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100-days incidence of CMV infection
Tidsramme: From date of CMV-CTLs infusion to 100 days after transplant
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Viral load >200 copies in 1 sample |
From date of CMV-CTLs infusion to 100 days after transplant
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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1-year incidence of CMV specific antiviral drug use
Tidsramme: From date of CMV-CTLs infusion to 1 year after transplant
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If viral load >200 copies in 2 samples or >1000 in 1 sample, treatment with valganciclovir will be started. Time from CMV-CTLs infusion until valganciclovir start and days of valganciclovir. |
From date of CMV-CTLs infusion to 1 year after transplant
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1-year incidence of CMV disease
Tidsramme: From date of CMV-CTLs infusion to 1 year after transplant
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CMV disease P.Lungman criteria. CMV as primary cause of death. |
From date of CMV-CTLs infusion to 1 year after transplant
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Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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1-year incidence of CMV-CTLs adverse events
Tidsramme: From date of CMV-CTLs infusion to 1 year after transplant
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Infusion reactions, causes of death, secondary graft failures and graft versus host disease (GVHD). |
From date of CMV-CTLs infusion to 1 year after transplant
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CMV-CTLs persistence
Tidsramme: From date of CMV-CTLs infusion to 2 months after infusion
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Expansion of CMV-CTLs detected by flow cytometry. |
From date of CMV-CTLs infusion to 2 months after infusion
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Immune reconstitution post-HAPLO
Tidsramme: From date of transplant to day 180 post-transplant
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CD3, CD4, CD8, B and NK lymphocyte counts in patient peripheral blood post-transplant (day 30, 60, 90 and 180) detected by flow cytometry. |
From date of transplant to day 180 post-transplant
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Samarbeidspartnere og etterforskere
Etterforskere
- Studieleder: Galo Peralta Fernandez, MD, Instituto de Investigación Marqués de Valdecilla
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- INMUNOCELL
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