Ignite Creation Date:
2024-07-17 @ 11:39 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06475820
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-26
First Post:
2024-05-17
Brief Title:
Preventing of GVHD With Post-transplantation Cyclophosphamide Abatacept Vedolizumab and Baricitinib at Children and Young Adults With Hemoblastosis
Sponsor:
Federal Research Institute of Pediatric Hematology Oncology and Immunology
Organization:
Federal Research Institute of Pediatric Hematology Oncology and Immunology
Study Overview
Official Title:
Prospective Pilot Study of the Clinical Efficacy and Safety of the Method for Preventing a Graft-versus-host Disease Through the Agency of Using the Combination of Post-transplantation Cyclophosphamide With Abatacept Vedolizumab and Baricitinib at Children and Young Adults With Hemoblastosis After Hematopoietic Stem Cell Transplantation From an Unrelated or Haploidentic Donor
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
GVHD prevention using a combination of post-transplantation cyclophosphamide in combination with abatacept vedolizumab and and Baricitinib in children and young adults with hematoloblastosis after myeloablative conditioning regimen with treosulfanTBI cyclophosphamideetoposide fludarabine after HSCT from matched unrelated and haploidentical donors
Detailed Description:
Conditioning regimen
Treosulfan 42 gm2course on the days -5 -4 -3 or total body irradiation 12 Graycourse on the days -8 -7 -6 Etoposide 60 mgkg on the days -6 -5 Fludarabine 150 mgm2course on the days -6 -5 -4 -3 -2
Prevention of GVHD
Cyclophosphamide 80 mgkgcourse on the days 3 4 Abatacept 10 mgkgday on the days 5 14 28 60 90 Vedolizumab 10 mgkgday max 300 mg on the days 0 14 28 60
Baricitinib 4 mgday per os patient age 9 years 2 mgday patient age 9 years from day -3 to day 90 after HSCT orally once a day
Donor selection criteria
In case of detection of two or more suitable donors the choice is made in favor of
CMV Compliance
Sex of donor and recipient
medical and psychological suitability and desire of the donor
Compatibility by blood type
Duration of therapy
120 days for patients with high risk of recurrence positive minimal residual disease before HSCT non-remission status after HSCT patients diagnosed with juvenile myelomonocytic leukemia
180 days for the rest Time of observation
follow up during 3 years after HSCT
Criteria for premature stopping of the study
1 The probability of developing acute GVHD II-IV is above 40 of which III-IV - above 15
2 The probability of 100-day transplant-associated mortality is higher than 20 Goal Evaluation Date Intermediate analysis after 1 year from the beginning The final analysis is scheduled to take place 100 days after the last patient is included
Data Monitoring and Management
1 Plan of initial examination of the patient
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
60 180 days after HSCT - for patients with MRD or refractory before HSCT MRD immunophenotyping Cytogenetics if it presence 3 Minimal residual disease MRD monitoring in patients with AML
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
4 Biobanking KM blood
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
CD348 TCRgd CD34845RACCR7 CD197 CD343145RA CD425127
NK-compartment
CD3CD56
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
Pathogen-specific immunoreconstitution research - ELISPOT method for evaluating the production of gamma-interferon by peripheral blood mononuclears after incubation with microbial antigens The main antigens studied are CMV pp65 EBV Adenovirus AdvHexon BK virus Multiplicity of analysis of recipients 30 60 100 180 360 The amount of blood for analysis on 30 days is 10 ml subsequently - 5 ml in a test tube with EDTA
Virological monitoring by PCR weekly
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
Biobanking Multiplicity 30 60 100 180 360 Blood in a test tube with EDTA used 2 Toxicity monitoring
Diagnosis and therapy of acute GVHD Clinical diagnosis and staging of acute GVHD is carried out in accordance with standard criteria Appendix No 3
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 ORTPH 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
Treosulfan 42 gm2course on the days -5 -4 -3 or total body irradiation 12 Graycourse on the days -8 -7 -6 Etoposide 60 mgkg on the days -6 -5 Fludarabine 150 mgm2course on the days -6 -5 -4 -3 -2
Prevention of GVHD
Cyclophosphamide 80 mgkgcourse on the days 3 4 Abatacept 10 mgkgday on the days 5 14 28 60 90 Vedolizumab 10 mgkgday max 300 mg on the days 0 14 28 60
Baricitinib 4 mgday per os patient age 9 years 2 mgday patient age 9 years from day -3 to day 90 after HSCT orally once a day
Donor selection criteria
In case of detection of two or more suitable donors the choice is made in favor of
CMV Compliance
Sex of donor and recipient
medical and psychological suitability and desire of the donor
Compatibility by blood type
Duration of therapy
120 days for patients with high risk of recurrence positive minimal residual disease before HSCT non-remission status after HSCT patients diagnosed with juvenile myelomonocytic leukemia
180 days for the rest Time of observation
follow up during 3 years after HSCT
Criteria for premature stopping of the study
1 The probability of developing acute GVHD II-IV is above 40 of which III-IV - above 15
2 The probability of 100-day transplant-associated mortality is higher than 20 Goal Evaluation Date Intermediate analysis after 1 year from the beginning The final analysis is scheduled to take place 100 days after the last patient is included
Data Monitoring and Management
1 Plan of initial examination of the patient
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
60 180 days after HSCT - for patients with MRD or refractory before HSCT MRD immunophenotyping Cytogenetics if it presence 3 Minimal residual disease MRD monitoring in patients with AML
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
4 Biobanking KM blood
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
CD348 TCRgd CD34845RACCR7 CD197 CD343145RA CD425127
NK-compartment
CD3CD56
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
Pathogen-specific immunoreconstitution research - ELISPOT method for evaluating the production of gamma-interferon by peripheral blood mononuclears after incubation with microbial antigens The main antigens studied are CMV pp65 EBV Adenovirus AdvHexon BK virus Multiplicity of analysis of recipients 30 60 100 180 360 The amount of blood for analysis on 30 days is 10 ml subsequently - 5 ml in a test tube with EDTA
Virological monitoring by PCR weekly
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
Biobanking Multiplicity 30 60 100 180 360 Blood in a test tube with EDTA used 2 Toxicity monitoring
Diagnosis and therapy of acute GVHD Clinical diagnosis and staging of acute GVHD is carried out in accordance with standard criteria Appendix No 3
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 ORTPH 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None