Clinical trial NCT04056533: Prophylaxis of Cytomegalovirus Infection With Adoptive Cell Inmunotherapy
Official title: Anti-CMV Pilot Clinical Trial: Prophylaxis of Cytomegalovirus Infection in Haploidentical Transplatation of Hematopoietic Progenitors With Adoptive Cell Inmunotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: CMV
Keywords: Citomegalovirus
Haploidentical
Hematopoietic Stem Cell Transplantation
Lead sponsor: Instituto de Investigación Marqués de Valdecilla
Sponsor class: OTHER
First posted: 2019-08-14
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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:

  1. HLA haploidentical and CMV-seropositve donors.
  2. Donor must be checked and suitable.
  3. Signed writen informed consent.
  4. 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.

Primary outcomes:
measure: 100-days incidence of CMV infection
timeFrame: From date of CMV-CTLs infusion to 100 days after transplant
Secondary outcomes:
measure: 1-year incidence of CMV specific antiviral drug use
timeFrame: From date of CMV-CTLs infusion to 1 year after transplant
measure: 1-year incidence of CMV disease
timeFrame: From date of CMV-CTLs infusion to 1 year after transplant
Other outcomes:
measure: 1-year incidence of CMV-CTLs adverse events
timeFrame: From date of CMV-CTLs infusion to 1 year after transplant
measure: CMV-CTLs persistence
timeFrame: From date of CMV-CTLs infusion to 2 months after infusion
measure: Immune reconstitution post-HAPLO
timeFrame: From date of transplant to day 180 post-transplant
Locations:
city: Santander
country: Spain
facility: Hospital Marques de Valdecilla
Study officials:
affiliation: Instituto de Investigación Marqués de Valdecilla
name: Galo Peralta Fernandez, MD
role: STUDY_DIRECTOR
References: