Prophylaxis of Cytomegalovirus Infection With Adoptive Cell Inmunotherapy (INMUNOCELL)

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

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.

Study Overview

• Status: Recruiting
• Conditions: CMV
• Intervention / Treatment: Biological: CMV CTLs

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 Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Miriam Sanchez-Escamilla, MD; Phone Number: +34646393234; Email: msanchez@idival.org
• Study Contact Backup: Name: Lucía Lavín Alconero, Phd; Email: eclinicos5@idival.org

Study Locations

• Spain
  • Santander, Spain
    • Recruiting
    • Hospital Marques de Valdecilla
    • Contact: enrique ocio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CMV CTLs; 1x10^5 CMV-CTLs/kg

Biological: 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year incidence of CMV-CTLs adverse events	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
CMV-CTLs persistence	Expansion of CMV-CTLs detected by flow cytometry.	From date of CMV-CTLs infusion to 2 months after infusion
Immune reconstitution post-HAPLO	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

Collaborators and Investigators

• Sponsor: Instituto de Investigación Marqués de Valdecilla
• Investigators: Study Director: Galo Peralta Fernandez, MD, Instituto de Investigación Marqués de Valdecilla

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2022
• Primary Completion (Anticipated): March 1, 2025
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: August 13, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (Actual): August 14, 2019

Study Record Updates

• Last Update Posted (Actual): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Haploidentical; Hematopoietic Stem Cell Transplantation; Citomegalovirus
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections
• Other Study ID Numbers: INMUNOCELL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No