Irradiation-based Myeloablative Conditioning Followed by Treg/Tcon Immunotherapy in HSCT

Study Overview
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Brief Summary
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To evaluate if hyper-fractionated TBI or TMLI followed by Treg/Tcon adoptive immunotherapy improve cGvHD/disease free survival after allogeneic HSCT in patients affected by high-risk acute leukemias or other hematologic malignancy where HSCT is indicated.

Detailed Description
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Improving cGvHD/disease free survival in patients with high-risk acute leukemias or other hematologic malignancy where HSCT is indicated with the use of a regulatory T cell based protocol. Hyper-fractionated Total Body Irradiation or Total Marrow and Lymphoid Irradiation based conditioning will be followed by the infusion of T regulatory and T conventional cell adoptive immunotherapy and a purified CD34+ hematopoietic stem cell graft. Incidence of Non Relapse Mortality, Relapse, acute Graft versus Host Disease, chronic Graft versus Host Disease, as well as probability of cGvHD/disease free survival will be assessed in patient subpopulations separated according to HLA-matching with the donor (HLA-matched HSCT and HLA-haploidentical HSCT) and type of disease (acute myeloid leukemia, acute lymphoid leukemia, lymphoma, multiple myeloma, myeloproliferative disease, and other).

Official Title
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Antileukemic Activity of Allogeneic Hematopoietic Stem Cell Transplantation With Fractionated Total Body Irradiation or Total Marrow and Lymph Node Irradiation Followed by Adoptive Immunotherapy With Regulatory and Conventional T Cells

Conditions
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Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Myeloproliferative Disorders, Lymphoma, Multiple Myeloma, Other Hematologic Malignant Neoplasms

Intervention / Treatment
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* Biological: High dose irradiation conditioning + Treg/Tcon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AML and ALL in complete remission and with high-risk of relapse AML and ALL primarily chemoresistant or relapsed; Chronic Myeloid Leukemia in accelerated or blastic phase; Patients affected by Multiple myeloma, Non Hodgkin lymphoma, Hodgkin lymphoma, Chronic myeloproliferative syndrome, Chronic Lymphoid Leukemia, Other Hematological malignancy at high-risk of relapse or detectable disease and where a HSCT is indicated. Age <75 years ECOG ≤ 2 Acceptable lung, liver, kidney, and heart function and absence of relevant psichiatric diseases Signature of the informed consent Exclusion Criteria: Age >75 years ECOG > 2 Not acceptable lung, liver, kidney, and heart function and presence of relevant psichiatric diseases Pregnancy No signature of the informed consent

Ages Eligible for Study
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Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose irradiation conditioning + Treg/Tcon<br>High dose irradiation based conditioning regimens followed by infusion of donor regulatory and conventional T cells and purified CD34+ hematopoietic stem cell transplantation | Biological: High dose irradiation conditioning + Treg/Tcon<br>* High dose irradiation based conditioning regimens followed by infusion of donor regulatory and conventional T cells and purified CD34+ hematopoietic stem cell transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| chronic GvHD/relapse-free survival | To evaluate if irradiation based myeloablative conditioning followed by Treg/Tcon adoptive immunotherapy improve chronic GvHD/relapse-free survival (GRFS) after allogeneic HSCT in patients affected by acute leukemias or other hematologic malignancies where HSCT is indicated. GRFS will be assessed in subgroups of patients separated according to HLA-matching with the donor and type of disease (acute myeloid lekemia, acute lymphoid leukemia, other) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| full donor-type engraftment | neutrophil and platelet engraftment measured by neutrophil counts >500/mmc for 3 consecutive days and platelets count >20000/mmc with 7 consecutive without platelet transfusion | 30 days |