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

NCT06756152 | Recruiting Phase 2

• 1 other identifier: NCHPOI-2024-10
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Biphenotypic Acute Leukemia; Acute Lymphoblastic Leukemia; Myeloblastic Leukemia; Bilinear Leukemia; Malignant Lymphoma, Non-Hodgkin; Myelodysplastic Syndrome

Keywords

Hematopoetic stem cell transplantation; posttransplant cyclophosphamide; vedolizumab; hematoblastosis; ALL; AML

Outcome Measures

Primary Outcomes (5)

• 1. Cumulative Incidence stage II-IV after HSCT

  Estimate the probability of developing acute GVHD stage II-IV after HSCT-

  up to 100 days

• Kaplan Meier overal survival

  Explore the safety based on an assessment of the frequency of occurrence severe (3-5 degrees) side effects of conditioning- 100-day transplant-associated mortality

  up to 100 days

• 1. Cumulative Incidence stage II-IV after HSCT

  Estimate the probability of developing acute GVHD stage II-IV after HSCT

  up to 100-day

• Kaplan Meier event free survival

  Explore the safety based on an assessment of the frequency of occurrence severe (3-5 degrees) side effects of conditioning

  during 1 month

• Kaplan Meier event free survival

  Explore the safety based on an assessment of the frequency of occurrence severe (3-5 degrees) side effects of conditioning- 100-day transplant-associated mortality

  up to 100 days

Secondary Outcomes (9)

• event-free survival

  up to 100 days

• Cumulative Incidence of leukocyte engraftment

  up to 30 days

• Cumulative Incidence of platelet engraftment

  up to 30 days

• Cumulative Incidence reactivation of CMV

  up to 6 mouth or up to immunreconstitution

• box plot

  up to 1 year

Study Arms (1)

Prevention of GVHD: Cyclophosphamide, Abatacept, Vedolizumab, Ruxolitinib

EXPERIMENTAL

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

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

Interventions

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

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.

Prevention of GVHD: Cyclophosphamide, Abatacept, Vedolizumab, Ruxolitinib

Eligibility Criteria

• Age: 1 Day - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead

Study Sites (1)

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

Moscow, 117198, Russia

RECRUITING

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelomonocytic, Acute; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes

Interventions

Etoposide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Lymphoma; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Central Study Contacts

Maschan Michael,, MD, PhD

CONTACT

+79166512145; mmaschan@yandex.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: January 1, 2025
• Study Start: July 10, 2024
• Primary Completion (Estimated): July 10, 2026
• Study Completion (Estimated): October 10, 2026
• Last Updated: January 1, 2025

Record last verified: 2024-12

Locations

RU (1)