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 (SHARP)

March 1, 2025 updated by: Antonio Pierini, University Of Perugia

SHARP - 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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

51

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
    • PG
      • Perugia, PG, Italy, 06100
        • Recruiting
        • Università degli Studi di Perugia
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TMLI based contioning and Treg/Tcon adoptive immunotherapy in allogeneic cell transplantation
All enrolled patients will receive a 20Gy-TMLI based conditioning regimen followed by the infusion of donor graft and Treg/Tcon adoptive immunotherapy
Radiation: total marrow/lymphoid irradiation
Combination of 20 Gy TMLI with Treg/Tcon adoptive immunotherapy in allogeneic cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants free from disease 2 years after HSCT
Time Frame: 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.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants that have reached engraftment 45 days after HSCT
Time Frame: 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.
45 days
Number of participants that developed grade ≥ 2 acute GvHD
Time Frame: 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.
2 years
Number of participants free from chronic GvHD 2 years after HSCT
Time Frame: 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.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Of Perugia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 25, 2025

Primary Completion (Estimated)

January 1, 2029

Study Completion (Estimated)

January 1, 2031

Study Registration Dates

First Submitted

February 14, 2025

First Submitted That Met QC Criteria

February 19, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 1, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHARP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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