ALLOGENEIC CD4+ AND CD8+ T LYMPHOCYTES EX VIVO INCUBATED WITH SYNTHETIC PEPTIDES OF THE VIRAL ANTIGENS OF CYTOMEGALOVIRUS, ADENOVIRUS AND EPSTEIN-BARR VIRUS for Cytomegalovirus (CMV) infection|Epstein-Barr virus (EBV) infection|Adenovirus (AdV) infection

Inclusion criteria

• {"criterion_text":"- Adult or paediatric patients (>2 months of age) after HSCT (no time restrictions apply) suffering from new or reactivated CMV or EBV or AdV infection, refractory to standard antiviral treatment for two weeks (defined as ≤1 log decrease in viral load over two weeks) as confirmed by quantitative blood PCR analysis\n- Original HSCT-donor available with an immune response at least to the virus causing the therapy-refractory (=underlying) infection\n- Written informed consent given (patient or legal representative)"}

Exclusion criteria

• {"criterion_text":"- Acute GvHD > grade II or extensive chronic GvHD at time of IMP transfer\n- Female patient who is pregnant or breast-feeding, or adult of reproductive potential not willing to use an effective method of birth control from Screening until the last follow-up visit (FU6, Visit 8) Note: women of childbearing potential must have a negative serum pregnancy test at study entry\n- Known hypersensitivity to iron dextran\n- Patients unwilling or unable to comply with the protocol or unable to give informed consent\n- Treatment with steroids (>1 mg/kg Prednisone equivalent) at Screening\n- Therapeutic donor lymphocyte infusion (DLI) from 4 weeks prior to IMP infusion until 8 weeks post IMP infusion. In case of T-cell depleted HSCT, a prescheduled prophylactic DLI ≤3 x 10^5 T cells/kg BW is not considered an exclusion criteria.\n- Organ dysfunction or failure as determined by Karnofsky (age >16 years) or Lansky (age ≤16 years) score ≤30%\n- Concomitant enrolment in another clinical trial interfering with the endpoints of this study\n- Any medical condition which could compromise participation in the study according to the investigator’s assessment\n- Progression of underlying disease (disease that has led to the indication of HSCT, e.g. leukaemia) that will limit the life expectance below the duration of the study\n- Second line or experimental antiviral treatment other than Ganciclovir/Valganciclovir, Foscarnet, Cidofovir and Rituximab from Screening until 8 weeks after IMP infusion or prophylactic treatment other than Aciclovir or Letermovir throughout the study except approved by sponsor\n- Known HIV infection. In case patients do not have a negative HIV test performed within 6 months before enrolment in the study, HIV negativity has to be confirmed by a negative laboratory test"}

Primary endpoints

• {"endpoint_text":"- Percentage of patients with viral clearance (defined as two consecutive negative PCRs)","definition_or_measurement_approach":"Viral clearance defined as two consecutive negative PCRs (quantitative blood PCR analysis)."}
• {"endpoint_text":"- Percentage of patients with progression between Day 7 and Week 8 after IMP transfer","definition_or_measurement_approach":"Proportion of patients with disease progression assessed between Day 7 and Week 8 after IMP transfer (time window Day 7 to Week 8)."}

Secondary endpoints

• {"endpoint_text":"- Incidence/severity of acute GvHD ≥ grade II until Week 8 and Week 15.","definition_or_measurement_approach":"Incidence and severity of acute graft-versus-host disease (GvHD) ≥ grade II assessed up to Week 8 and Week 15."}
• {"endpoint_text":"- Incidence of newly occurring acute GvHD grade I from Day 0 to Week 8 and Week 15.","definition_or_measurement_approach":"Incidence of new acute GvHD grade I between Day 0 and Week 8 and Week 15."}
• {"endpoint_text":"- Incidence of chronic GvHD from Day 7 to Week 8 and to Week 15 after IMP transfer.","definition_or_measurement_approach":"Incidence of chronic GvHD assessed from Day 7 to Week 8 and to Week 15 after IMP transfer."}
• {"endpoint_text":"- Time to newly occurring acute and chronic GvHD.","definition_or_measurement_approach":"Time-to-event measurement: time from reference (Day 0 or specified baseline) to onset of new acute or chronic GvHD."}
• {"endpoint_text":"- Acute toxicity: maximum toxicity on the day of IMP transfer evaluated by measuring vital signs prior to and at different times after the IMP transfer and monitoring of specific adverse events (chills, nausea, vomiting, diarrhoea, abdominal pain, allergic reactions, respiratory dysfunction or headache from 1 hour prior to IMP transfer to 4 hours post infusion).","definition_or_measurement_approach":"Assessment of maximum acute toxicity on day of IMP transfer by serial vital signs and monitoring of specified adverse events from 1 hour prior to IMP transfer to 4 hours post-infusion."}
• {"endpoint_text":"- Change in viral load of underlying viral infection as assessed by quantitative PCR analysis of peripheral blood; samples taken weekly from Day 7 to Week 8 after IMP transfer as compared to samples taken at Day 0.","definition_or_measurement_approach":"Quantitative PCR analysis of peripheral blood viral load; weekly samples from Day 7 to Week 8 compared with Day 0."}
• {"endpoint_text":"- Time to 1 log change in viral load.","definition_or_measurement_approach":"Time (days) to achieve a 1 log change in viral load as measured by quantitative PCR."}
• {"endpoint_text":"- Percentage of patients with ≥1 log decrease in CMV, EBV or AdV viral load at Week 8.","definition_or_measurement_approach":"Proportion of patients achieving ≥1 log decrease in viral load for CMV, EBV or AdV at Week 8 (quantitative PCR)."}
• {"endpoint_text":"- Number of reactivations of the underlying viral infection following initial viral clearance until end of follow-up.","definition_or_measurement_approach":"Count of viral reactivations after initial viral clearance until end of follow-up, assessed by PCR and clinical criteria."}
• {"endpoint_text":"- Number of patients with reduction or clearance of clinical symptoms of underlying viral infection from Day 7 to Week 8 after IMP transfer as compared to Day 0.","definition_or_measurement_approach":"Number/proportion of patients with reduction or resolution of clinical symptoms between Day 7 and Week 8 compared to Day 0 (clinical assessment)."}
• {"endpoint_text":"- Overall survival rate (OS): From Day 0 to end of follow-up.","definition_or_measurement_approach":"Overall survival measured from Day 0 to end of follow-up (time-to-event)."}
• {"endpoint_text":"- Number of days requiring antiviral chemotherapy after IMP transfer from Day 7 to Week 8 after IMP transfer.","definition_or_measurement_approach":"Count of days on antiviral chemotherapy between Day 7 and Week 8 after IMP transfer."}
• {"endpoint_text":"- Time to last administration of defined antiviral medication or switch to prophylactic treatment from Day 0 to Week 8 after IMP transfer.","definition_or_measurement_approach":"Time from Day 0 to last administration of defined antiviral or switch to prophylactic treatment up to Week 8."}
• {"endpoint_text":"- Number of new viral reactivations (CMV, AdV or EBV) other than the underlying viral infection per patient as assessed by PCR analysis and clinical symptoms throughout the study.","definition_or_measurement_approach":"Per-patient count of new viral reactivations (CMV, AdV, EBV) identified by PCR and clinical symptoms during entire study."}
• {"endpoint_text":"- Number of days hospitalized after IMP transfer from Day 7 to Week 8.","definition_or_measurement_approach":"Number of hospitalization days recorded between Day 7 and Week 8 after IMP transfer."}
• {"endpoint_text":"- EQ-5D and FACT-BMT for adult patients (≥18 years), and PEDS-QL for paediatric patients (<18 years) at Screening and Week 8.","definition_or_measurement_approach":"Health-related quality of life: EQ-5D and FACT-BMT for adults, PEDS-QL for paediatric patients, measured at Screening and Week 8."}
• {"endpoint_text":"- T-cell phenotyping, samples taken at Screening, Day 0 and each visit from Day 7 to Week 15 after IMP transfer.","definition_or_measurement_approach":"Immunophenotyping of T cells on peripheral blood samples at Screening, Day 0 and scheduled visits from Day 7 to Week 15."}
• {"endpoint_text":"- Analysis of virus-specific T cells: frequencies of in vivo expanded virusspecific T cells in peripheral blood samples taken at Screening, Day 0, Day 7 to Week 15 after IMP transfer.","definition_or_measurement_approach":"Frequency assessment of virus-specific T cells in peripheral blood samples at Screening, Day 0 and Days 7 through Week 15."}
• {"endpoint_text":"- Assessment of the number and viability of CD3+ cells and percentage of IFNgamma+ cells and cellular composition in the IMP.","definition_or_measurement_approach":"Quality control of IMP: enumeration and viability of CD3+ cells, percentage IFN-gamma+ cells and cellular composition measured in the investigational medicinal product."}
• {"endpoint_text":"- Drop-out rate at Day 0 and reasons for drop-out.","definition_or_measurement_approach":"Drop-out proportion at Day 0 and documented reasons for withdrawal."}
• {"endpoint_text":"- Number of days from Screening to Day 0 (day of IMP transfer).","definition_or_measurement_approach":"Duration in days from Screening visit to Day 0 (IMP transfer)."}
• {"endpoint_text":"- Documentation of incidence, severity and type of adverse events from Day 0 to Week 8 and serious adverse events throughout the study.","definition_or_measurement_approach":"Recording and classification (incidence, severity, type) of AEs from Day 0 to Week 8 and SAEs throughout the trial."}
• {"endpoint_text":"- Physical examination and vital signs from Screening to Week 8; Karnofsky/Lansky index will be assessed at Screening and at Week 8.","definition_or_measurement_approach":"Serial physical exams and vital signs from Screening to Week 8; Karnofsky/Lansky performance scores at Screening and Week 8."}
• {"endpoint_text":"- Laboratory values for clinical chemistry and haematology from Screening to Week 8.","definition_or_measurement_approach":"Clinical chemistry and hematology laboratory parameters measured from Screening through Week 8."}
• {"endpoint_text":"- Documentation of all concomitant medication from Screening to Week 8.","definition_or_measurement_approach":"Recording of all concomitant medications administered from Screening to Week 8."}
• {"endpoint_text":"- During follow-up Week 15, only antiviral therapy, immunosuppression and SAErelated concomitant medication as well as chemotherapy will be documented.","definition_or_measurement_approach":"At Week 15 follow-up, documentation limited to antiviral therapy, immunosuppression, SAE-related concomitant meds and chemotherapy."}
• {"endpoint_text":"- Non-therapeutic DLI has to be documented as concomitant medication (definition see exclusion criteria).","definition_or_measurement_approach":"Documentation of non-therapeutic donor lymphocyte infusion (DLI) as concomitant medication per protocol definition."}
• {"endpoint_text":"- Treatment with T cells after Week 8 will also be documented as concomitant medication.","definition_or_measurement_approach":"Any T-cell treatment administered after Week 8 recorded as concomitant medication."}

Belgium

Earliest CTIS Part Ii Submission Date

23-06-2024

Latest Decision Or Authorization Date

02-07-2024

Processing Time Days

9

Number Of Sites

2

Number Of Participants

12

France

Earliest CTIS Part Ii Submission Date

23-06-2024

Latest Decision Or Authorization Date

10-07-2024

Processing Time Days

17

Number Of Sites

4

Number Of Participants

12

Italy

Earliest CTIS Part Ii Submission Date

23-06-2024

Latest Decision Or Authorization Date

07-08-2024

Processing Time Days

45

Number Of Sites

1

Number Of Participants

31

Netherlands

Earliest CTIS Part Ii Submission Date

23-06-2024

Latest Decision Or Authorization Date

02-07-2024

Processing Time Days

9

Number Of Sites

1

Number Of Participants

22

Germany

Earliest CTIS Part Ii Submission Date

23-06-2024

Latest Decision Or Authorization Date

08-07-2024

Processing Time Days

15

Number Of Sites

10

Number Of Participants

34

Primary sponsor

Full Name

Medical Center - University Of Freiburg

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany