Clinical trial to assess the effect of virus-specific activated T lymphocytes from a donor in hematopoietic progenitor transplanted patients
- Conditions
- CMV viral infection in an immunocompromised hostMedDRA version: 20.0Level: LLTClassification code 10021819Term: Infection in marrow transplant recipientsSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2018-000911-25-ES
- Lead Sponsor
- Banc de Sang i Teixits
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 20
1. Recipient of an allogeneic hematopoietic progenitors cell transplant (irrespectively of the donor source, donor type conditioning and underlying disease) that is beyond the day +30 of the procedure
2. Patient with post-transplant infection due to CMV refractory or resistant to optimal pharmacological treatment. Specifically, the patient must be included in any of the following cases
a) Patient with organic disease caused by CMV (confirmed by histology) resistant to antiviral first line treatment
b) Patient with CMV reactivation and no organic disease, resistant or intolerant to 2 previous antiviral treatment lines (ganciclovir/valganciclovir and foscarnet) or not candidate to be treated due to not acceptable expected toxicity (severe renal insufficiency, neutropenia or severe thrombopenia)
It is agreed that the patient is affected with a resistant CMV infection if the CMV copies doesn’t decrease in > 1 log in total blood or otherwise the absolute number of copies > 1x10E4/mL in total blood after 2 weeks of antiviral treatment.
c) Patients with reactivation of recurrent CMV despite correct anti-CMV treatment.
It will be considered a recurrent CMV infection if the patient has> 2 reactivations in a period <6 months despite having received correct anti-CMV treatment
d) Documented genetic mutations associated with ganciclovir or foscarnet resistance
3. = 1 year of age
4. Estimated life expectancy > 30 days
5. Signature of the informed consent form
Are the trial subjects under 18? yes
Number of subjects for this age range: 9
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1
1.Acute GVHD = grade II or chronic = moderate
2.Corticosteroid = 0.5mg/kg regardless the indication
3.Disease relapse at the time of infection or at any time after the Allogeneic transplant.
4.Severe renal disease (creatinine > 3gr/dL)
5.Severe hepatic disease (bilirrubine >3mg/dL or AST >500 U/L) except if it is secondary to the viral infection.
6.Having received a donor lymphocytes infusion or any cell therapy product within 60 days prior to inclusion in the study (with the exception of transfusions), or having it planned within the next 60 days.
7.Alteration of the general condition, infection or clinical or hemodynamic instability that, in the opinion of the researcher, does not recommend the use of T cells
8.Known hypersensitivity to murine proteins or iron dextran.
9.Positive serology to HIV, HBV (HBsAg, HBcAc), HCV and/or syphilis
10.Pregnant, lactating or women without adequate contraception (*)
11.Participation in a clinical trial with investigational medicinal products the last 30 days
(*) The effective contraceptive methods contemplated in the protocol are the hormonal ones, intrauterine device (IUD), barrier methods, voluntary sterilization or females with menopause > 1 year of duration.
The criteria should be reviewed once the donor has been selected and before proceeding to the donor's lymphoapheresis to confirm that the patient is still a candidate for treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. To evaluate the safety of ViroTCell administration to the recipient in the post-transplant period;Secondary Objective: 1-Efficacy of the ViroTCell infusion for the treatment of infection assessed by Viral Load (PCR) and Clinical assessment<br>2-Immune reconstitution ability aginst virus <br>3-Persistence studies of virus-specific T cells using chimerism techniques <br>4-Time elapsed until a donor is identified;Primary end point(s): -Safety assessment through physical examination, vital signs, laboratory data and adverse events. The development of acute GVHD will be measured by the Seattle modified criteria;Timepoint(s) of evaluation of this end point: +7, +14, +21, +28, +45, +60 days
- Secondary Outcome Measures
Name Time Method Secondary end point(s): -PCR quantitative viral load for CMV at +7, +14, +21, +28, +45, +60 days<br>-Immune reconstitution against CMV using Elispot at +7, +14, +28, +60 days<br>-Immune reconstitution against CMV by flow cytometry at +7, +14, +28, +60 days<br>-T-cell persistence by chimerism: detection of donor cellularity (administered product) in the receptor serum at +14 y +28 days<br>-Time elapsed in identifying the donor. The type of donor available at the time of patient’s inclusion, the type of donor finally selected and the time elapsed from the inclusion of the patient to the date of selection of the donor (date of the stimulation test of the selected donor).;Timepoint(s) of evaluation of this end point: +7, +14, +21, +28, +45, +60 days