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

NCT06845592 | Recruiting DMC

• 1 other identifier: SHARP
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

AML; ALL; SHARP; Total marrow/lymphoid irradiation; Treg; Tcon; Relapse

Outcome Measures

Primary Outcomes (1)

• Number of participants free from disease 2 years after HSCT

  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 Outcomes (3)

• Number of participants that have reached engraftment 45 days after HSCT

  45 days

• Number of participants that developed grade ≥ 2 acute GvHD

  2 years

• Number of participants free from chronic GvHD 2 years after HSCT

  2 years

Study Arms (1)

TMLI based contioning and Treg/Tcon adoptive immunotherapy in allogeneic cell transplantation

EXPERIMENTAL

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

Interventions

total marrow/lymphoid irradiation RADIATION

Combination of 20 Gy TMLI with Treg/Tcon adoptive immunotherapy in allogeneic cell transplantation

TMLI based contioning and Treg/Tcon adoptive immunotherapy in allogeneic cell transplantation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Of Perugia: lead

Study Sites (1)

Università degli Studi di Perugia

Perugia, PG, 06100, Italy

RECRUITING

Related Publications (63)

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MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Interventions

Lymphatic Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics

Central Study Contacts

Antonio Pierini

CONTACT

+393355477611; antonio.pierini@unipg.it

Loredana Ruggeri

CONTACT

+393388953982; loredana.ruggeri@ospedale.perugia.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A Simon's Minimax two-stage design has been chosen for predicting number of patients and duration of the study. Such design allows the investigator to early stop patient enrollment in case of unexpected futility.

Study Record Dates

• First Submitted: February 14, 2025
• First Posted: February 25, 2025
• Study Start: February 25, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2031
• Last Updated: March 4, 2025

Record last verified: 2025-02

Locations

IT (1)