Primary prophylaxis of CMV infection in haploidentical transplantation of hematopoietic progenitors. MedDRA version: 20.0 Level: HLGT Classification code 10025309 Term: Haematological and lymphoid tissue therapeutic procedures System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 21.1 Level: PT Classification code 10063581 Term: Stem cell transplant System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 22.0 Level: PT Classification code 100678
Conditions
Interventions
Product Name: Cytolityc T Lymphocytes
Pharmaceutical Form: Infusion
INN or Proposed INN: CYTOMEGALOVIRUS-SPECIFIC T-CELLS
Current Sponsor code: Donor-specific anti-CMV CTLs
Other descriptive name: CYT
Sponsors
IDIVAL
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: PRE-inclusion criteria Patients must meet all of the criteria below to participate in the study: Adult patients (over 18 years of age), whether or not diagnosed with haematological malignancy, who have received an allogeneic haematopoietic progenitor transplant from haploidentical family donors (HAPLO). 2. Any source of hematopoietic progenitors for transplantation. 3. Patients whose original haploidenetic donor is seropositive CMV (IgG positive antibodies and IgM negative in CMV serology). 4. Negative pregnancy test in women. 5. Informed consent in writing signed by the patient or legal representative. DONORS: a. Donors will be selected if they meet haploidentical HLA criteria with the patient and are CMV seropositive (Ig G positive antibodies and Ig M negative in CMV serology). b. The donor will be screened to determine if it is SUITABLE according to the evaluation criteria of hematopoietic progenitor donors. c. The donor must sign the informed written consent prior to inclusion. d. The donor must NOT have evidence of active infection at the time of lymphocyte apheresis. CRITERIA OF INCLUSION/INFUSION (the inclusion is made prior to the day of infusion, which will take place on the 21st post-HAPLO day +-7 days) Recovery of the post-HAPLO hematopoietic implant at least partially: i. Partial recovery: Absolute count of neutrophils > 0.5x10^9 cells/L for at least 3 consecutive post-HAPLO determinations. ii. Complete recovery: In addition to neutrophil count, platelet count > 20 x 10^9/L independent of transfusions at least 7 days. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: Patients must NOT meet any of the criteria below to participate in the study: 1. Patients who do not have a CMV-positive haploidenetic donor. 2. Patients who are unable to perform the follow-up or visits described for the trial. Infusion will NOT be performed if the patient meets any of the following criteria: i. Patients in treatment, at the time of infusion with doses of corticosteroids greater than 0.5mg/kg/day of prednisone or equivalent. ii. ECOG > or = 3. iii. Organic toxicity higher than grade 3 according to CTCAE Version 5.0. iv. Patients who have received anti-thymocyte globulin (ATG), donor lymphocyte infusion (ILD) or alemtuzumab within 28 days prior to infusion. v. Patients with uncontrolled infection defined by fever and/or hemodynamic instability and/or unresolved infectious focus. vi. Fever persistent in the 3 days prior to infusion. vii. Patients with acute graft-versus-receptor disease (GVHD), grade II-IV. viii. Active and uncontrolled relapse or progression of malignant disease. ix. A viral reactivation of CMV prior to the day of infusion (21 post-HAPLO) requiring anti-viral treatment (more than 200 copies of CMV per PCR). Patients who do not meet the infusion criteria after the 28th post-HAPLO day will be removed from the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 1. To evaluate the need for treatment for CMV a. Need for anti-CMV treatment b. Time to next anti-CMV treatment c. Duration of anti-CMV treatment 2. To Evaluate the incidence of CMV disease a.Incidence of CMV disease b. Direct mortality per CMV 3. SECURITY a. To evaluate the appearance of immediate (200 copies in 1 determination (PCRq)).;Timepoint(s) of evaluation of this end point: The timepoint is 12 months for the recruitment and 12 months for Follow up;Main Objective: To evaluate the efficacy of antiviral prophylaxis with specific CTLs against CMV in reducing the incidence of CMV infection at 100 days post-transplant HAPLO, according to historical controls of the haematology service of the Hospital Universitario Marqués de Valdecilla. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary variables of efficacy are: 1. Assessing the need for treatment for CMV a. Need for anti-CMV treatment: If viral load>200 copies in 2 determinations or more than 1000 copies in 1 determination, treatment with valganciclovir will be initiated. b. Time to next anti-CMV treatment from the day of transplant. c. Duration of anti-CMV treatment (days). 2. Assess the incidence of CMV disease a. Incidence of CMV disease: criteria for CMV disease (P.Ljungman et al, Lancet Infect Dis 2019). b. Direct CMV mortality: primary cause of CMV death.;Timepoint(s) of evaluation of this end point: Safety evaluations (variables and parameters) To assess the occurrence of immediate (<24h) or delayed infusional reactions using the infusion adverse reaction questionnaire. | — |
Countries
Spain
Contacts
Public ContactLucía Lavín/María del Mar García
IDIVAL
Outcome results
None listed