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)

University Of Perugia

Status: Enrolling

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

Treatments: Radiation: total marrow/lymphoid irradiation

Study type: Interventional

Funder types: Other

Identifiers

NCT06845592

SHARP

Details and patient eligibility

About

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.

Enrollment: 51 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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51 participants in 1 patient group

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

Experimental group

Description:

All enrolled patients will receive a 20Gy-TMLI based conditioning regimen followed by the infusion of donor graft and Treg/Tcon adoptive immunotherapy

Treatment:

Radiation: total marrow/lymphoid irradiation