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.
Conditions
Interventions
Product Name: donor derived antiviral T cells (CMV)
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Donor Derived Anti-viral T cells (CMV)
Other descriptive name: HUMAN CYTOMEGALOVI
Sponsors
Ghent University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients o Disease and disease characteristics: all patients with underlying diseases that form an indication for allogeneic stem cell transplantation. o Major 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 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
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 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 o Any condition not fulfilling inclusion criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • The primary objective of this clinical trial is double. • First, starting from the patients and donors that fulfill all inclusion criteria and do not have any exclusion criterium, and donors fulfilling all pre-apheresis criteria (including a sufficient number of circulating CMV-specific T-cells, based on the in vitro test described below), we will evaluate the percentage of patients for whom we can manufacture a product that meets release criteria, and can therefore receive the product. • Second, we will evaluate the safety of the administered cell product. We want to evaluate the frequency of patients who develop de novo or recurrent (with a history of (completely recovered)) acute GVHD grade 2 or more or show worsening of an existing aGVHD with at least 1 grade, or emergence of an additional organ involved. ;Secondary Objective: • To evaluate the clinical efficacy of this treatment in these patients. • To evaluate infusion related toxicity of the infused T cells, within the first 48 hours after infusion. • To explore the relationship between the presence of CMV specific T cells in the peripheral blood of the patient and the objective clinical response. • To make the treatment of relapsing or refractory CMV infection after allogeneic stem cell transplantation with CMV-specific T cell therapy from the CMV positive donor available for patients in Belgium • To compare resistance to antiviral therapy in both arms (investigational vs observational). ;Primary end point(s): • We have identified 2 primary endpoints. • First, we have set up a technical endpoint. Starting from the patients and donors that fulfill all inclusion criteria and do not have any exclusion criterium, and donors fulfilling all pre-apheresis criteria (including a sufficient number of circulating CMV-specific T-cells, based on the in vitro test described below), we want to evaluate the percentage of products that meet release criteria, and can therefore be administered to the patie | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To evaluate the clinical efficacy of this treatment in eligible patients having eligible donors, by comparing outcome in both investigational and observational arm, as evidenced by: - Initial response: o significant effect (decrease in CMV PCR with at least 1 log on at least 2 consecutive measurements) or o complete resolution of the CMV infection (CMV PCR below detection limit for at least 2 consecutive times) - Duration of the response (after 1month, 3 months, 6 months and 1 year): the incidence of reactivation of CMV infection after the first good response after T cell administration, which will reflect the in vivo longevity of the administered cells. - Duration of antiviral therapy (total duration and starting from the inclusion in the observational vs investigational arm, respectively). - Prevention of new reactivations (frequency of reactivations and duration of reactivation/CMV PCR positivity). • To evaluate the infusional toxicity of the infused T cells, within the first 72 hours after infusion: clinically (symptoms and clinical signs by means of a check list) and lab results): fever, cytokine storm. • To explore the relationship between the presence (and expansion) of CMV specific T cells (absolute number) in the peripheral blood of the patient and the objective clinical response, as measured on week 1, 4 and 8 post infusion. • To compare resistance to antiviral therapy in both arms (investigational vs observational). ;Timepoint(s) of evaluation of this end point: up to 1 year after administration | — |
Countries
Belgium
Contacts
Public ContactBimetra Clinics
Ghent University Hospital
Outcome results
None listed