Safely Delivered Targeted High-dose Irradiation Followed by Adoptive Immunotherapy with Regulatory and Conventional T Cells to Increase Potency of Hematopoietic Stem Cell Transplantation in High-risk Acute Leukemia

Not Applicable

Recruiting

• Conditions: Acute Myeloid Leukaemia (AML); Acute Lymphoblastic Leukemia ALL; High Risk Leukaemia; Leukaemia Relapse

• Registration Number: NCT06845592
• Lead Sponsor: University Of Perugia

Brief Summary

The study is a monocentric, interventional study that evaluates the efficacy of allogeneic HLA-matched or haploidentical transplantation consisting of an irradiation-based conditioning regimen coupled with donor Treg/Tcon adoptive immunotherapy for high-risk acute leukemia patients.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-14
• Study First Submitted QC: 2025-02-19
• Study Start: 2025-02-25
• Study First Posted: 2025-02-25
• Last Update Submitted: 2025-03-01
• Last Update Posted: 2025-03-04
• Primary Completion: 2029-01
• Study Completion: 2031-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

• AML patients

  • Diagnosis of AML with indication to allogeneic hematopoietic cell transplantation.
  • Diagnosis of adverse genetic risk leukemia or presence of MRD or active disease (bone marrow infiltration 5-30%) at the time of the transplant procedure.
  • Availability of a hematopoietic stem cell donor (family or unrelated HLA-matched or HLA-haploidentical with the patient) suitable to be treated with G-CSF (10 mcg/kg/die) for a maximum of 7 days and able to tolerate 2 or more leukaphereses.
  • Age ≥ 18 and ≤ 65 years
  • ECOG ≤ 2
  • HCT-CI ≤ 4 (51,52)
  • Absence of relevant psychiatric diseases
  • Signature of the informed consent

ALL patients

• Diagnosis of ALL, either T or B (Philadelphia negative) or mixed phenotype with indication to allogeneic transplant
• Presence of MRD or active disease (bone marrow infiltration 5-30%) or patient with ≥ 2nd complete hematologic remission at the time of the transplant procedure.
• Availability of a hematopoietic stem cell family donor (family or unrelated HLA-matched or HLA-haploidentical with the patient) suitable to be treated with G-CSF (10 mcg/kg/die) for a maximum of 7 days and able to tolerate 2 or more leukaphereses.
• Age ≥ 18 and ≤ 65 years
• ECOG ≤ 2
• HCT-CI ≤ 4
• Absence of relevant psychiatric diseases
• Signature of the informed consent

Exclusion Criteria

• AML patients

  • AML in CR MRD-
  • AML with > 5% peripheral blasts or bone marrow infiltration ≥ 30%
  • Age < 18 years or > 65 years
  • ECOG > 2
  • Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment
  • Pregnancy
  • No signature of the informed consent

• ALL patients

  • ALL with > 5% peripheral blasts or bone marrow infiltration ≥30%
  • Philadelphia positive ALL
  • Age < 18 years or > 65 years
  • ECOG > 2
  • Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment
  • Pregnancy
  • No signature of the informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Number of participants free from disease 2 years after HSCT	2 years	The primary objective of the study is to reduce the incidence of disease relapse after irradiation-based conditioning regimen and Treg/Tcon adoptive immunotherapy-based allogeneic transplantation from HLA-matched or haploidentical donors in high-risk acute leukemia patients.

Secondary Outcome Measures

Name	Time	Method
Number of participants that have reached engraftment 45 days after HSCT	45 days	The study will also evaluate the impact of the allogeneic transplantation from HLA-matched or haploidentical donors with irradiation-based conditioning regimen and Treg/Tcon adoptive immunotherapy on major transplantation outcomes in high-risk acute leukemia patients such as full donor type engraftment.
Number of participants that developed grade ≥ 2 acute GvHD	2 years	The study will also evaluate the impact of the allogeneic transplantation from HLA-matched or haploidentical donors with irradiation-based conditioning regimen and Treg/Tcon adoptive immunotherapy on major transplantation outcomes in high-risk acute leukemia patients such as grade ≥ 2 acute GvHD.
Number of participants free from chronic GvHD 2 years after HSCT	2 years	The study will also evaluate the impact of the allogeneic transplantation from HLA-matched or haploidentical donors with irradiation-based conditioning regimen and Treg/Tcon adoptive immunotherapy on major transplantation outcomes in high-risk acute leukemia patients such as chronic GvHD.

Trial Locations

Locations (1)

Università degli Studi di Perugia; 🇮🇹 Perugia, PG, Italy