Prophylaxis of Cytomegalovirus Infection With Adoptive Cell Inmunotherapy

NCT ID: NCT04056533

Last Updated: 2024-08-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-26
• Study Completion Date: 2026-12-01

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.

Conditions

CMV

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

CMV CTLs

1x10\^5 CMV-CTLs/kg

Group Type: EXPERIMENTAL

CMV CTLs

Intervention Type: BIOLOGICAL

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.

Interventions

CMV CTLs

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.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Investigación Marqués de Valdecilla

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Galo Peralta Fernandez, MD

Role: STUDY_DIRECTOR

Instituto de Investigación Marqués de Valdecilla

Locations

Hospital Marques de Valdecilla

Santander, , Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Miriam Sanchez-Escamilla, MD

Role: CONTACT

msanchez@idival.org

+34646393234

Lucía Lavín Alconero, Phd

Role: CONTACT

eclinicos5@idival.org

Facility Contacts

enrique ocio

Role: primary

Other Identifiers

INMUNOCELL

Identifier Type: -

Identifier Source: org_study_id