Trial Title:
Preventing of GVHD With Post-transplantation Cyclophosphamide, Abatacept, Vedolizumab and Calcineurin Inhibitor at Patients With Hemoblastosis
NCT ID:
NCT05515029
Condition:
Acute Lymphoblastic Leukemia
Myeloblastic Leukemia
Biphenotypic Acute Leukemia
Malignant Lymphoma
Myelodysplastic Syndromes
Juvenile Myelomonocytic Leukemia
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myelomonocytic, Juvenile
Lymphoma
Leukemia, Biphenotypic, Acute
Myelodysplastic Syndromes
Cyclophosphamide
Abatacept
Vedolizumab
Calcineurin Inhibitors
Conditions: Keywords:
Hematopoetic stem cell transplantation
posttransplant cyclophosphamide
vedolizumab
AML
ALL
children
graf versus host disease
adolescents
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Combination Product
Intervention name:
GVHD prevention: post-transplantation cyclophosphamide, abatacept, vedolizumab, calcineurin inhibitor
Description:
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
Arm group label:
GVHD prevention: post-transplantation cyclophosphamide, abatacept, vedolizumab,calcineurin inhibitor
Summary:
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
Detailed 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:
- 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:
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.
- 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 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
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Patients under the age of 21 years with following diseases:
- acute lymphoblastic,
- myeloblastic,
- biphenotypic,
- bilinear leukemia,
- malignant lymphoma,
- myelodysplastic syndrome,
Exclusion Criteria:
- Age over 21 years
- Patients with ALL outside clinical and hematological remission
- Clinical status:
- Lansky/Karnowski index <70%
- Heart function: left ventricular ejection fraction <40% according to ultrasound
of the heart1
- Kidney function: clearance of endogenous creatinine < 70 ml / min
- Liver function: total bilirubin, ALT, AST, ALP > 2 norms
- Lung function: lung capacity <50%, for children who cannot carry out of
respiratory function - oxygen saturation during pulse oximetry <92%
- 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
Gender:
All
Minimum age:
1 Day
Maximum age:
21 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology
Address:
City:
Moscow
Zip:
11198
Country:
Russian Federation
Start date:
August 23, 2022
Completion date:
October 16, 2026
Lead sponsor:
Agency:
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Agency class:
Other
Source:
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05515029
