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GVHD prevention using a combination of post-transplantation cyclophosphamide in combination with abatacept, vedolizumab and calcineurin inhibitor in children and young adults with hematoloblastosis after myeloablative conditioning regimen with treosulfan/TBI, cyclophosphamide/etoposide, fludarabine after HSCT from matched unrelated and haploidentical donors
Full description
Conditioning regimen:
Treosulfan 42 g/m2/course on the days -5, -4, -3 or total body irradiation 12 Gray/course on the days -8, -7, -6 Cyclophosphamide 50 mg/kg/course on the days -3, -2 or Etoposide 60 mg/kg on the days -6, -5 Fludarabine 150 mg/m2/course on the days -6, -5, -4, -3, -2
Prevention of GVHD:
Cyclophosphamide 100 mg/kg/course on the days +3, +4 Abatacept 10 mg/kg/day on the days +5, +14, +28, +45, +60, +90, +120 Vedolizumab 10 mg/kg/day, max. 300 mg on the days -1, +14, +28 Cyclosporine A or Tacrolimus 3 mg/kg/day from -1 to 120 (in case of high risk of relapse: patients with JMML, without of remission o positive MRD after HSCT)/180 days or Ruxolitinib (in case of intolerance to calcineurin inhibitors) 5m/day for patients <12 years old and 10 mg/day for patients >12 years old by scheme of CNI.
Donor selection criteria
In case of detection of two or more suitable donors, the choice is made in favor of:
Duration of therapy
Criteria for premature stopping of the study
Data Monitoring and Management
After signing the informed consent and registration, the patient undergoes an examination in accordance with the standard plan of pre-transplantation examination and additional examinations, including:
Confirmation of remission status, determination of MRD, chimerism according to the protocol 1. Monitoring of donor chimerism in patients with acute leukemia Point Days Lines
1 +30 day general, CD34
Only if a relapse of the disease is suspected, cm can be sent to study chimerism:
General
Chimerism in the sorted MRD fraction 2. Minimal residual disease (MRD) monitoring in patients with ALL +30, +100 days after HSCT - for all patients: MRD (immunophenotyping), Cytogenetics (if it presence)
+100 days after HSCT - for all patients: MRD (immunophenotyping), Cytogenetics (if it presence)
30, +180 days after HSCT - for patients with MRD + or refractory before HSCT: MRD (immunophenotyping), Cytogenetics (if it presence)
In this protocol, in addition to routine post-transplantation monitoring, the following studies are carried out:
• Study of the subpopulation composition of peripheral blood lymphocytes: B-cells: CD19
T-cells:
CD3/4/8/ TCR/gd CD3/4/8/45RA/CCR7 (CD197) CD3/4/31/45RA CD4/25/127
NK-compartment:
CD3/CD56
TCR repertoire:
Analysis multiplicity: +30, +60, +100, +180, +360 day The amount of blood for analysis is 5 ml in a test tube with EDTA.
Blood: CMV, EBV, ADV by PCR method Chair: ADV MONITORING by PCR is carried out up to 100 days after CGSC. The exception is patients with viremia, or receiving immunosuppressive therapy on day 100.
in case of suspected visceral lesion: cerebrospinal fluid / bal / stool / urine / biopsy / other material
When an isolated rash appears, a skin biopsy is mandatory. When a clinic of acute GVHD appears with damage to the upper and lower gastrointestinal tract (nausea, vomiting, enterocolitis), gastroscopy with a biopsy of the gastric mucosa and colonoscopy with a floor biopsy is reokended.
The biopsy material should also be sent for virological examination. Before starting therapy, a consultation is held with the head of the protocol / appointed expert.
• Criteria for prescribing systemic immunosuppressive therapy: Acute GVHD stage I - therapy is not carried out Acute GVHF stage II-IV - methylprednisolone 1-2 mg / kg / day IV The period for assessing the response to first-line therapy: 72 hours, 7 days, 14 days from the start of therapy.
• Criteria for prescribing second-line therapy: progression of manifestations of O.RTPH after 72 hours or no improvement after 7 days or incomplete resolution of clinical and laboratory manifestations after 14 days
• Diagnosis and therapy of chronic GVHD: Diagnosis and staging of chronic GVHD are performed in accordance with THE NIH criteria (Appendix No. 4). Due to the fact that the development of chronic GVHD is one of the main parameters for the evaluation of the study, the diagnosis and staging of chronic GVHD are performed prospectively, monthly from the day +100, using a structured examination in accordance with Appendix No. 2.
Therapy of chronic GVHD is carried out in accordance with the standard adopted in the clinic
Enrollment
Sex
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Volunteers
Inclusion criteria
Patients under the age of 21 years with following diseases:
Exclusion criteria
Age over 21 years
Patients with ALL outside clinical and hematological remission
Clinical status:
Uncontrolled viral, fungal or bacterial infection.
Mental illness of the patient or caregivers, making it impossible to realize the essence of the study and compromising compliance with medical appointments and sanitary and hygienic regime 1 These patients may receive treatment according to the protocol, but the results will be evaluated separately
Primary purpose
Allocation
Interventional model
Masking
56 participants in 1 patient group
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Central trial contact
Mikchail Maschan, PD; Elena f Smirnova
Data sourced from clinicaltrials.gov
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