Prophylaxis of Cytomegalovirus Infection With Adoptive Cell Inmunotherapy

CMV Clinical Trial

— INMUNOCELL  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04056533
• Other study ID #: INMUNOCELL
• Status: Recruiting
• Phase: Phase 2
• Start date: March 26, 2022
• Est. completion date: March 1, 2026

Study information

• Verified date: September 2021
• Source: Instituto de Investigación Marqués de Valdecilla
• Contact: Miriam Sanchez-Escamilla, MD
• Phone: +34646393234
• Email: msanchez[@]idival.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: March 1, 2026
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• CMV
• Cytomegalovirus Infections

Intervention

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.

Locations

Country	Name	City	State
Spain	Hospital Marques de Valdecilla	Santander

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigación Marqués de Valdecilla

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	CMV-CTLs persistence	Expansion of CMV-CTLs detected by flow cytometry.	From date of CMV-CTLs infusion to 2 months after infusion
Other	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
Primary	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	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
Secondary	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