Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04056533
Other study ID # INMUNOCELL
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
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
Health authority
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 donĀ“t fill infusion criteria, after day 28 post-HAPLO, will be considered screening failures and will be out of the study.

Study Design


Related Conditions & MeSH terms


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
See also
  Status Clinical Trial Phase
Enrolling by invitation NCT04101136 - Effect of Atorvastatin on Subclinical Atherosclerosis N/A
Recruiting NCT06001320 - De-novo Initiation of Letermovir vs Valganciclovir for Cytomegalovirus Prophylaxis in AA Kidney Trans Recip Early Phase 1
Completed NCT01923766 - Cytotoxic T Cells to Prevent Virus Infections Phase 1
Not yet recruiting NCT05969743 - Letermovir Prophylaxis for Cytomegalovirus (CMV) in Patients With Graft-versus-host Disease Phase 2
Recruiting NCT01011712 - The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
Recruiting NCT06034925 - Maribavir vs. Valganciclovir for CMV Prophylaxis in High-Risk Kidney Transplant Recipients Phase 4
Completed NCT04840199 - A Study to Evaluate the Anti-inflammatory Effects of Letermovir (Prevymis) in Adults With Human Immunodeficiency Virus (HIV)-1 and Asymptomatic Cytomegalovirus (CMV) Who Are on Suppressive Antiretroviral Therapy, Plus Its Effect on Chronic Inflammation, HIV Persistence and Other Clinical Outcomes. Phase 2
Terminated NCT03502161 - Clinical Evaluation of the QuantiFERON CMV Assay
Not yet recruiting NCT06211543 - Letermovir (LMV) Prophylaxis in CMV-seronegative Allogeneic Stem Cell Transplant Recipients With CMV Seropositive Donors: an Exploratory Study From Spanish GETH/TC Centers
Not yet recruiting NCT04280380 - Cytomegalovirus Infection in Critically Ill Patients and Patients Receiving Anticancer Therapy
Active, not recruiting NCT03924219 - CMV T Cell Immunity in Pediatric Solid Organ Transplant Recipients
Not yet recruiting NCT06453460 - Prospect Eval of Efficacy of CMV-TCIP Direct Letermovir Prophylax After Allogen Hemato Cell Transpla Phase 2
Completed NCT02694484 - Search Cytomegalovirus in Healthy Volunteers Stools Samples Selected as Potential Donor for Fecal Microbiota Transplant N/A
Recruiting NCT06011486 - Expansion of Virus-Specific Lymphocytes for Cell Therapy Phase 1
Recruiting NCT04017962 - A Study of the Drug Letermovir (LTV) as Prevention for Recurrent of Cytomegalovirus (CMV) Infection Phase 2
Terminated NCT03570411 - Evaluating the Clinical Utility of the T-SPOT.CMV Assay for the Prediction of CMV Reactivation Among Pediatric Patients Undergoing Hematopoietic Cell Transplant
Enrolling by invitation NCT04392297 - Clinical and Immunological Features of the CMV Infection Atypical Course in Immunocompetent Individuals
Completed NCT00872703 - Does Normal Brain Imaging Predict Normal Neurodevelopmental Outcome in Fetuses With Proven Cytomegalovirus Infection? N/A
Active, not recruiting NCT01945814 - Allogeneic Multivirus - Directed Cytotoxic T Lymphocytes (CTL) Phase 1
Recruiting NCT05041426 - Letermovir for CMV Prevention After Lung Transplantation Phase 2