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Prophylaxis of Cytomegalovirus Infection With Adoptive Cell Inmunotherapy (INMUNOCELL)

Primary Purpose

CMV

Status

Recruiting

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

CMV CTLs

About this trial

This is an interventional prevention trial for CMV focused on measuring Citomegalovirus, Haploidentical, Hematopoietic Stem Cell Transplantation

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Hospital Marques de ValdecillaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CMV CTLs

Arm Description

1x10^5 CMV-CTLs/kg

Outcomes

Primary Outcome Measures

100-days incidence of CMV infection

Viral load >200 copies in 1 sample

Secondary Outcome Measures

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.

1-year incidence of CMV disease

CMV disease P.Lungman criteria. CMV as primary cause of death.

Full Information

NCT ID

NCT04056533

First Posted

August 13, 2019

Last Updated

May 5, 2022

Sponsor

Instituto de Investigación Marqués de Valdecilla

1. Study Identification

Unique Protocol Identification Number

NCT04056533

Brief Title

Prophylaxis of Cytomegalovirus Infection With Adoptive Cell Inmunotherapy

Acronym

INMUNOCELL

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Recruiting

Study Start Date

March 26, 2022 (Actual)

Primary Completion Date

March 1, 2025 (Anticipated)

Study Completion Date

March 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Instituto de Investigación Marqués de Valdecilla

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

CMV

Keywords

Citomegalovirus, Haploidentical, Hematopoietic Stem Cell Transplantation

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CMV CTLs

Arm Type

Experimental

Arm Description

1x10^5 CMV-CTLs/kg

Intervention Type

Biological

Intervention Name(s)

CMV CTLs

Intervention Description

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.

Primary Outcome Measure Information:

Title

100-days incidence of CMV infection

Description

Viral load >200 copies in 1 sample

Time Frame

From date of CMV-CTLs infusion to 100 days after transplant

Secondary Outcome Measure Information:

Title

1-year incidence of CMV specific antiviral drug use

Description

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.

Time Frame

From date of CMV-CTLs infusion to 1 year after transplant

Title

1-year incidence of CMV disease

Description

CMV disease P.Lungman criteria. CMV as primary cause of death.

Time Frame

From date of CMV-CTLs infusion to 1 year after transplant

Other Pre-specified Outcome Measures:

Title

1-year incidence of CMV-CTLs adverse events

Description

Infusion reactions, causes of death, secondary graft failures and graft versus host disease (GVHD).

Time Frame

From date of CMV-CTLs infusion to 1 year after transplant

Title

CMV-CTLs persistence

Description

Expansion of CMV-CTLs detected by flow cytometry.

Time Frame

From date of CMV-CTLs infusion to 2 months after infusion

Title

Immune reconstitution post-HAPLO

Description

CD3, CD4, CD8, B and NK lymphocyte counts in patient peripheral blood post-transplant (day 30, 60, 90 and 180) detected by flow cytometry.

Time Frame

From date of transplant to day 180 post-transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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: HLA haploidentical and CMV-seropositve donors. Donor must be checked and suitable. Signed writen informed consent. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Miriam Sanchez-Escamilla, MD

Phone

+34646393234

msanchez@idival.org

First Name & Middle Initial & Last Name or Official Title & Degree

Lucía Lavín Alconero, Phd

eclinicos5@idival.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Galo Peralta Fernandez, MD

Organizational Affiliation

Instituto de Investigación Marqués de Valdecilla

Official's Role

Study Director

Facility Information:

Facility Name

Hospital Marques de Valdecilla

City

Santander

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

enrique ocio

12. IPD Sharing Statement

Learn more about this trial

Prophylaxis of Cytomegalovirus Infection With Adoptive Cell Inmunotherapy

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