CMV specific T cell therapy for the treatment of relapsing or therapy refractory CMV infection after allogeneic stem cell transplantation with a CMV-positive donor.

Phase 1

• Conditions: CMV specific T cell therapy for the treatment of relapsing or therapy refractory CMV infection after allogeneic stem cell transplantation with a CMV-positive donor.; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2013-004953-26-BE
• Lead Sponsor: Ghent University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-03-21
• Last Update Posted: 17 March 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Patients
oDisease and disease characteristics: all patients with underlying diseases that form an indication for allogeneic stem cell transplantation.
oMajor inclusion criteria:
?Male or female; fertile patients must use a reliable contraception method
?Age 16-75 yrs (the goal is to extend this study in a later stage to children <16yrs, but this will be submitted as an amendment to this trial or as a new clinical trial, depending on the accrual rate and interim analysis)
?Underwent allogeneic stem cell transplantation with a donor that fulfills the following criteria:
oCMV-seropositive donor (at the time of transplant)
oAge 18-70 yrs
?Having a CMV reactivation or primary infection (in case of a CMV negative patient pre transplant) or disease (with symptoms, including fever and/or symptoms of organ involvement, eg lungs or intenstine) with the following characteristics
oCMV PCR at least twice positive AND
oCMV infection relapsing after 3 successful treatment episodes with gancyclovir (first choice and only reimbursed treatment in Belgium) OR
oRefractory to treatment with available antiviral drugs (ganciclovir, valganciclovir, foscarnet or combinations - valganciclovir, foscarnet are not reimbursed for this indication in Belgium, so treatment is only possible through medical need programs or after special consent of the mutuality, which is only seldom possible), which is defined as follows:
?Persistent positive CMV PCR > detection limit 14 days after initiation of antiviral treatment or
?Increasing CMV viral load 7 days after initiation of antiviral treatment or
?Informed consent given by patient or his/her guardian if indicated.

Donor
1.Donor is identical to donor of the previous stem cell transplant
2.Donor has positive IgG serology for CMV, IgM negative or positive
3.Donor has signed informed consent for the donation of donor lymphocyte cells (available worldwide)
4.Donor is found fit for donation by a medical doctor according to selection criteria conform KB annex II (C-2009/18414)
5.Donor is negative for infectious disease markers including HCV, HBV and HIV-NAT testing: HBs antigen, HBc/HBs antibodies, Syphilis (TPHA or equivalent), HCV and HIV antibodies.
6.Additional testing should be performed and negative when relevant: malaria, west nile virus, trypanosomiasis, HTLV conform KB annex II (C-2009/18414)
In addition, the donor will be pre-screened for the presence of sufficient numbers of CMV-specific T cells.:
1.Interferon-gamma producing T cells upon CMVpp65 stimulation are at least twice background levels (=unstimulated cells)
2.At least 10 events of Interferon-gamma positive T cells are measured
3.Interferon-gamma producing T cells upon CMVpp65 stimulation are equal or higher than 0.1% of the viable CD4+ and CD8+ cell population

Are the trial subjects under 18? yes
Number of subjects for this age range: 2
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 6

Exclusion Criteria

For the patients
-Any condition not fulfilling inclusion criteria
-HIV, HCV, HBV positive (of course patients who are HbSAg positive after vaccination are not excluded)
-Life expectancy severely limited by disease other than malignancy or viral infection;
-Administration of cytotoxic agent(s) for cytoreduction” within three weeks prior to initiating of the treatment or to be expected within 8 weeks after administration of the treatment
-Terminal organ failure (specific detailed descriptions for cardiac, pulmonary and hepatic failure available), except for renal failure (dialysis acceptable)
-Uncontrolled other infection than the one being treated
-Karnofsky Performance Score <60%
-Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment
-Patient is a female who is pregnant or breastfeeding
-Patient with active aGVHD grade 3 or more
-Patient with severe chronic GVHD
-Patient on corticosteroids > 0.5 mg/kg. Patient can still be on therapeutic doses of immunosuppressive therapy, but these will be tapered to the lowest possible dose, as is part of standard care in case of CMV reactivation.
-Patient that has received ATG <1m prior to infusion or Campath <1y prior to infusion.

For the donors
oAny condition not fulfilling inclusion criteria

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified