Prophylaxis of Cytomegalovirus Infection With Adoptive Cell Inmunotherapy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Anti-CMV Pilot Clinical Trial: Prophylaxis of Cytomegalovirus Infection in Haploidentical Transplatation of Hematopoietic Progenitors With Adoptive Cell Inmunotherapy

Conditions
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CMV

Intervention / Treatment
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* Biological: CMV CTLs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients who received an alogeneic stem cell transplantation from haploidentical donors (HAPLO). Any source of stem cells (peripheral blood or bone marrow). CMV-seropositive donors. Negative pregnancy test in women. Signed writen informed consent. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CMV CTLs<br>1x10^5 CMV-CTLs/kg | Biological: CMV CTLs<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 100-days incidence of CMV infection | Viral load >200 copies in 1 sample | From date of CMV-CTLs infusion to 100 days after transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year incidence of CMV specific antiviral drug use | 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 | 
| 1-year incidence of CMV disease | CMV disease P.Lungman criteria. CMV as primary cause of death. | From date of CMV-CTLs infusion to 1 year after transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Citomegalovirus, Haploidentical, Hematopoietic Stem Cell Transplantation