Prophylaxis of Cytomegalovirus Infection With Adoptive Cell Inmunotherapy

Phase 2

Recruiting

• Conditions: CMV
• Interventions: Biological: CMV CTLs

• Registration Number: NCT04056533
• Lead Sponsor: Instituto de Investigación Marqués de Valdecilla

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.

Study Timeline

• Study First Submitted: 2019-08-13
• Study First Submitted QC: 2019-08-13
• Study First Posted: 2019-08-14
• Study Start: 2022-03-26
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-27
• Last Update Posted: 2024-08-28
• Primary Completion: 2026-03-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CMV CTLs	CMV CTLs	1x10\^5 CMV-CTLs/kg

Primary Outcome Measures

Name	Time	Method
100-days incidence of CMV infection	From date of CMV-CTLs infusion to 100 days after transplant	Viral load \>200 copies in 1 sample

Secondary Outcome Measures

Name	Time	Method
1-year incidence of CMV specific antiviral drug use	From date of CMV-CTLs infusion to 1 year after transplant	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.
1-year incidence of CMV disease	From date of CMV-CTLs infusion to 1 year after transplant	CMV disease P.Lungman criteria. CMV as primary cause of death.

Trial Locations

Locations (1)

Hospital Marques de Valdecilla; 🇪🇸 Santander, Spain