RecruitingPhase 2Phase 3NCT06756152

Preventing of GVHD with Post-transplantation Cyclophosphamide, Abatacept, Vedolizumab and Ruxolitinib At Children and Young Adults with Hemoblastosis

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 Ruxolitinib At Children and Young Adults with Hemoblastosis After Hematopoietic Stem Cell Transplantation from an Unrelated or Haploidentic Donor


Sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Enrollment

50 participants

Start Date

Jul 10, 2024

Study Type

INTERVENTIONAL

Conditions

Summary

GVHD prevention using a combination of post-transplantation cyclophosphamide in combination with abatacept, vedolizumab and Ruxolitinib in children and young adults with hematoloblastosis after myeloablative conditioning regimen with treosulfan/TBI, etoposide, fludarabine after HSCT from matched unrelated and haploidentical donors


Eligibility

Min Age: 1 DayMax Age: 21 Years

Inclusion Criteria7

  • \. Patients under the age of 21 years with following diseases:
  • acute lymphoblastic,
  • myeloblastic,
  • biphenotypic,
  • bilinear leukemia,
  • malignant lymphoma,
  • myelodysplastic syndrome,

Exclusion Criteria10

  • Age over 21 years
  • Patients with ALL outside clinical and hematological remission
  • Clinical status:
  • Lansky/Karnowski index \<70% (supplement No.1)
  • 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

Interventions

DRUGConditioning regimen: Treosulfan 42 g/m2/course or total body irradiation 12 Gray/course, Etoposide 60 mg/kg , Fludarabine 150

The most significant adverse events limiting the use of HSCT from an unrelated donor are graft-versus-host disease (GVHD) and prolonged immunodeficiency associated with the development of severe infectious complications. The use of post-transplant cyclophosphamide for the prevention of GVHD during allogeneic HSCT from unrelated and haploidentical donors has reduced the incidence of acute clinically significant GVHD in children to 25%, chronic GVHD to 12-30%, but the issue of GVHD control still remains extremely relevant. Emerging data on the use of abatacept, a selective blocker of the costimulatory signal from an antigen-presenting cell, in the prevention of intestinal GVHD and data on the effectiveness of Janus-kinase type 1/2 inhibitors (JAK-1/2) in the treatment and prevention of acute GVHD allow us to justify the use of these drugs in combination with post-transplant cyclophosphamide as a promising pharmacological platform for the prevention of GVHD.


Locations(1)

National medical research center of pediatric haematology, oncology and immulogy named after Dmytriy Rogachyov

Moscow, Russia

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NCT06756152


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