Pilot Study of Haploidentical Donor Adenovirus Specific T-lymphocytes to Treat Refractory Adenovirus Infections

Official title

Open-Label Pilot Study of Haploidentical Donor Adenovirus Specific T Lymphocytes (ADV-VSTS) for the Treatment of Refractory Adenovirus Infection and/or Disease in Hospitalized Patients

Overview

This open-label, single-arm, phase I/II clinical trial will assess the safety and efficacy of related donor adenovirus-specific T lymphocytes isolated from whole blood or leukapheresis products. The adenovirus-specific T lymphocytes will be generated automatically by the CliniMACS Prodigy using the CliniMACS Cytokine Capture System (IFN-γ) after incubation with MACS GMP PepTivator Peptide Pools of Hexon 5 for enrichment.

Interventions

• Biological Adenovirus Specific T lymphocytes
  ADV-VSTs is being proposed for the treatment of refractory ADV infection and/or disease in these populations using haploidentical donors for ease of donor selection, antiviral immunity, coupled with a high-throughput antigen stimulation/IFN-γ capture system (Miltenyi Biotec, CliniMACS Prodigy® System) for rapid and less costly isolation of ADV-VSTs.

Primary outcome measures

• Safety by measuring unacceptable toxicities [Time frame: 7-28 days]
• Efficacy by measuring viral load [Time frame: 28 days]

Eligibility criteria

Inclusion criteria

• Age 0 days to 60 years with one of the following conditions:

• Patients who are solid organ transplantation recipients (renal, heart, lung, liver, pancreas, small bowel, multi-visceral) and are > 28 days post-transplant at the time of screening.
• Patients with underlying malignancy who are receiving or have received chemotherapy within 6 months of screening.
• Patients with known autoimmune or autoinflammatory conditions, not associated with a known underlying primary immunodeficiency
• Patients who are receiving or have received systemic immunosuppressive therapies in the 30 days prior to screening including: biologic agents, calcineurin inhibitors, mTOR inhibitors, or corticosteroid
• Patients without known immunocompromised conditions
• And must meet at least 1 of the following criteria.

• Documented ADV refractory infection (i.e., DNAemia detected by qualitative or quantitative PCR in the peripheral blood > 14 days or rising viral load in blood despite antiviral therapy >14 days).
• Evidence of refractory ADV end organ disease (proven or probable as previously defined46, including pneumonitis, colitis, hepatitis, hemorrhagic cystitis etc.) despite antiviral therapy >14 days.
• Medical intolerance to anti-viral therapies including renal toxicity (Cr >2) and/or bone marrow suppression (ANC <1500, Hb <10 and/or Plt <50) or gastrointestinal manifestation (grade ≥2 diarrhea), or other related organ injury.
• At high risk for antiviral failure due to history of recurrent ADV reactivations, or recently started on increased immunosuppressants.
• Negative pregnancy test in female patients if applicable (childbearing potential)
• Written informed consent and/or signed assent line from patient, parent or legal guardian prior to any study-related procedures.

Exclusion criteria

• Receipt of anti-thymocyte globulin (ATG), alemtuzumab, cytoxan, or other T-cell depleting drugs or monoclonal antibodies within 28 days from enrollment
• Receiving corticosteroid (prednisone equivalent) ≥ 0.5mg/kg/day or ≥ 20mg/day at the time of enrollment
• Recipients of allogeneic hematopoietic stem cell transplant (bone marrow, peripheral blood or umbilical cord blood)
• Evidence of uncontrolled infection (except ADV) as follows:

• Bacterial infections - patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment
• Fungal infections - patients must be receiving definitive systemic anti-fungal therapy and evidence of response/stabilization on therapy for 1 week prior to enrollment
• Progressing infection is defined as hemodynamic instability attributable to sepsis, or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection
• Patient with poor performance status determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30% (Table 5)
• Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory adenovirus infection(s)
• During the study, treatment with other investigational anti-adenoviral agents is prohibited until Week 12.
• If patient has been treated with CMX001 (brincidofovir, BCV) prior to ADV-VST enrollment, BCV must be discontinued for at least 72 hours prior to ADV-VSTs infusion for washout based on known geometric mean elimination half-life of BCV (8 to 12 hours). Any medical condition which could compromise participation in the study according to the investigator's assessment
• Known HIV infection
• Female patient of childbearing age who is pregnant or breast-feeding or not willing to use an effective method of birth control during study treatment.
• Known hypersensitivity to iron dextran
• Patients unwilling or unable to comply with the protocol or unable to give informed consent.
• Known human anti-mouse antibodies

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Nationwide Children's Hospital — Columbus

Identifiers

NCT: NCT04722029 · STUDY00001291

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗