Irradiation-based Myeloablative Conditioning Followed by Treg/Tcon Immunotherapy in HSCT
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
1 other identifier
interventional
80
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Feb 2014
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2014
CompletedFirst Submitted
Initial submission to the registry
June 4, 2019
CompletedFirst Posted
Study publicly available on registry
June 6, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
February 28, 2023
CompletedJanuary 13, 2020
January 1, 2020
9.1 years
June 4, 2019
January 8, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (1)
full donor-type engraftment
30 days
Other Outcomes (4)
cumulative incidence of grades ≥ 2 acute GvHD
6 months
cumulative incidence of extensive chronic GvHD
2 years
cumulative incidence of non-relapse mortality
2 years
- +1 more other outcomes
Study Arms (1)
High dose irradiation conditioning + Treg/Tcon
EXPERIMENTALHigh dose irradiation based conditioning regimens followed by infusion of donor regulatory and conventional T cells and purified CD34+ hematopoietic stem cell transplantation
Interventions
High dose irradiation based conditioning regimens followed by infusion of donor regulatory and conventional T cells and purified CD34+ hematopoietic stem cell transplantation
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Perugia
Perugia, PG, 06132, Italy
Related Publications (3)
Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, Del Papa B, Zei T, Ostini RI, Cecchini D, Aloisi T, Perruccio K, Ruggeri L, Balucani C, Pierini A, Sportoletti P, Aristei C, Falini B, Reisner Y, Velardi A, Aversa F, Martelli MF. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011 Apr 7;117(14):3921-8. doi: 10.1182/blood-2010-10-311894. Epub 2011 Feb 3.
PMID: 21292771BACKGROUNDMartelli MF, Di Ianni M, Ruggeri L, Falzetti F, Carotti A, Terenzi A, Pierini A, Massei MS, Amico L, Urbani E, Del Papa B, Zei T, Iacucci Ostini R, Cecchini D, Tognellini R, Reisner Y, Aversa F, Falini B, Velardi A. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014 Jul 24;124(4):638-44. doi: 10.1182/blood-2014-03-564401. Epub 2014 Jun 12.
PMID: 24923299BACKGROUNDPierini A, Ruggeri L, Carotti A, Falzetti F, Saldi S, Terenzi A, Zucchetti C, Ingrosso G, Zei T, Iacucci Ostini R, Piccinelli S, Bonato S, Tricarico S, Mancusi A, Ciardelli S, Limongello R, Merluzzi M, Di Ianni M, Tognellini R, Minelli O, Mecucci C, Martelli MP, Falini B, Martelli MF, Aristei C, Velardi A. Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for acute myeloid leukemia. Blood Adv. 2021 Mar 9;5(5):1199-1208. doi: 10.1182/bloodadvances.2020003739.
PMID: 33646302DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrea Velardi, MD, PhD
University Of Perugia
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Full Professor
Study Record Dates
First Submitted
June 4, 2019
First Posted
June 6, 2019
Study Start
February 1, 2014
Primary Completion
February 28, 2023
Study Completion
February 28, 2023
Last Updated
January 13, 2020
Record last verified: 2020-01