Clinical Trial for the Prevention of Cytomegalovirus Infection in Hematopoietic Stem Cell Transplantation in Patients with No Available Treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instituto De Investigacion Marques De Valdecilla

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2025-01-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-520020-28-00

EudraCT number

2019-002311-26

ClinicalTrials.gov

NCT04056533

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To evaluate the efficacy of antiviral prophylaxis with specific CTLs against CMV in reducing the incidence of CMV infection at 100 days posttransplant, according to historical controls of the haematology
service of the Hospital Universitario Marqués de Valdecilla

Secondary objectives 6

1. Efficiency: Assess the need for CMV treatment
2. Efficiency:Evaluate the incidence of CMV disease, its characteristics and mortality
3. Safety: Evaluate the occurrence of immediate (<24h) or delayed infusional reactions.
4. Safety: To evaluate the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), in terms of secondary attachment failure, XML File Identifier: UpbqLT1nsMdVMooHTktbNMVzXmA= Page 10/22 acute and chronic graft-versus-recipient disease (GVHD) and overall mortality.
5. Exploratory:To evaluate the persistence of allogeneic CMV-specific memory T lymphocytes by flow cytometry on the day of cell infusion (+-7 days) at 1 month and 2 months after hematopoietic progenitor infusion
6. Exploratory:To evaluate post-HAPLO immune reconstitution at day 30, 60, 90 and 180 post-TPH

Conditions and MedDRA coding

Cytomegalovirus infection post allogeneic allogeneic HLA-identical familial PHT

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Adult patients (over 18 years of age), whether or not diagnosed with hematologic malignancy, who have received an allogeneic HSCT hematopoietic progenitor transplant from HLA-identical family donors
2. Non-candidates to receive Letermovir
3. Source of HSC progenitors: peripheral blood or bone marrow
4. Patients whose donor is CMV seropositive
5. Negative pregnancy test in women
6. Written informed consent signed by the patient or legal representative
7. Partial recovery of the hematopoietic implant (absolute neutrophil count >0.5 x10^9 cells/L for at least 3 consecutive post-HSCT determinations)
8. Specific inclusion criteria for donors:
9. a. Donors will be selected if they meet HLA identity criteria and are CMV seropositive
10. b. The donor will be screened to determine suitability according to the HSCT hematopoietic progenitor donor evaluation criteria
11. C. The donor has to also sign a written informed consent prior to inclusion

Exclusion criteria 18

1. MUST NOT MEET ANY OF THE ESTABLISHED CRITERIA for the prescription of LETERMOVIR in CMV seropositive adult recipients of an allogeneic HSCT:
2. Related donor with at least one mismatch at one of the HLA locus (HLA-A, -B or -DR)
3. Haploidentical donor
4. Unrelated donor with at least one mismatch at one of the four HLA gene loci (HLA-A, -B, -C and -DRB1)
5. Use of cord blood
6. Use of graft with ex vivo T-lymphocyte depletion
7. GvHD grade 2 or higher requiring the use of systemic corticosteroids (doses ≥1mg/kg/day of prednisone or equivalent doses of other corticosteroids
8. AND MUST NOT MEET ANY OF THE CRITERIA BELOW to participate in the study:
9. Treatment at the time of cell infusion with corticosteroid doses greater than 0.5mg/kg/day of prednisone or equivalents
10. ECOG > or = 3
11. Organ toxicity greater than grade 3 according to CTCAE Version 5.0
12. Uncontrolled infection, defined by fever and/or hemodynamic instability and/or unresolved infectious focus.
13. Persistent fever (>38ºC) in the 3 days prior to the infusion
14. Relapse or active and uncontrolled progression of the malignant disease
15. CMV viral reactivation prior to the day of infusion (21 post-HSCT) requiring anti-viral treatment (more than 200 copies of CMV by PCR in 2 determinations or more than 1000 in 1 determination).
16. Previous therapy with Letermovir
17. Specific exclusion criteria for donors:
18. a. Active infection at the time of lymphoapheresis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. efficacy is the incidence of CMV infection AT DAY 100 POST-TPH (measured as viral load >200 copies in 2 determinations or >1000 in 1 determination [PCRq]).

Secondary endpoints 3

1. Assess the need for CMV treatment
2. To evaluate the incidence of CMV disease
3. to assess the presence of allogeneic CMV-specific memory T lymphocytes

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instituto De Investigacion Marques De Valdecilla

Sponsor organisation

Instituto De Investigacion Marques De Valdecilla

Address

Avenida Del Cardenal Herrera Oria S/n

City

Santander

Postcode

39011

Country

Spain

Scientific contact point

Organisation

Instituto De Investigacion Marques De Valdecilla

Contact name

mar garcia

Public contact point

Organisation

Instituto De Investigacion Marques De Valdecilla

Contact name

mar garcia

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications