Allogeneic HSCT in MDS Patients Based on Risk According to R-IPSS

Allogeneic Transplantation in Patients With Myelodysplastic Syndrome Based on Risk According to Revised-International Prognostic Scoring System (R-IPSS)

An "intention-to-treat" study to evaluate the impact of allogeneic HSCT with Total Marrow and Lymphoid irradiation (TMLI), followed by Treg/Tcon adoptive immunotherapy, on overall survival in patients affected by Myelodysplastic Syndrome (MDS), according to IPSS-R.

Study Overview

• Status: Recruiting
• Conditions: MDS and Allogeneic Stem Cell Transplantation
• Intervention / Treatment: Other: MDS and AlloHSCT

Detailed Description

MDS patients with Intermediate, High, or Very-High R-IPSS risk will be enrolled. Allogeneic stem cell transplantation with regulatory and conventional T cell adoptive immunotherapy will be proposed to eligible High and Very-High risk MDS patients. Intermediate risk MDS patients will be assessed for risk modification every six months and moved to transplant in case of increased risk. Intermediate risk MDS patients will be also evaluated for the presence of molecular alterations (TP53, ASXL1, RUNX1). Overall survival of the entire cohort will be assessed as primary endpoint. Incidence of Treatment Related Mortality, acute Graft versus Host Disease, chronic Graft versus Host Disease, Relapse will be also assessed.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Antonio Pierini, MD; Phone Number: +390755784147; Email: antonio.pierini@unipg.it
• Study Contact Backup: Name: Mara Merluzzi, MBioTech; Phone Number: +393482200239; Email: maramerluzzi@libero.it

Study Locations

• Italy
  • PG
    • Perugia, PG, Italy, 06132
      • Recruiting
      • University Of Perugia
      • Contact: Antonio Pierini, MD; Phone Number: +390755784147; Email: antonio.pierini@unipg.it
      • Contact: MERLUZZI MARA; Phone Number: +393482200239; Email: maramerluzzi@libero.it
      • Principal Investigator: Cristina Mecucci, MD
      • Principal Investigator: Cynthia Aristei, MD
      • Principal Investigator: Antonio Pierini, MD
      • Principal Investigator: Alessandra Carotti, MD
      • Sub-Investigator: Roberta La Starza, MD
      • Sub-Investigator: Loredana Ruggeri, MD
      • Sub-Investigator: Adelmo Terenzi, MD
      • Sub-Investigator: Chiara Camerini, MD
      • Sub-Investigator: Martina Quintini, MD
      • Sub-Investigator: Simonetta Saldi, MD
      • Sub-Investigator: Samanta Bonato, MD
      • Sub-Investigator: Mario Griselli, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients affected by Myelodysplastic Syndrome with IPSS-R INT, HIGH or VERY HIGH;
• Age <71 years;
• Signature of the informed consent.

Exclusion Criteria:

• Patients affected by Myelodysplastic Syndrome with IPSS-R VERY LOW or LOW;
• Patients affected by Myelodysplastic Syndrome/Myeloproliferative Neoplasm;
• Age >70 years;
• No signature of the informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: SINGLE ARM	Other: MDS and AlloHSCT; Allogeneic stem cell transplantation, based on TMLI and followed by infusion of donor regulatory T cells and conventional T cells and purified donor CD34+ hematopoietic stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	We will evaluate overall survival in patients with intermediate/High/very-High risk MDS	4 years

Collaborators and Investigators

• Sponsor: University Of Perugia
• Investigators: Principal Investigator: Andrea Velardi, MD, University Of Perugia

Publications and helpful links

General Publications

• 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.
• Martelli 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2019
• Primary Completion (Anticipated): September 19, 2025
• Study Completion (Anticipated): September 19, 2025

Study Registration Dates

• First Submitted: February 28, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 17, 2021
• Last Update Submitted That Met QC Criteria: March 11, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 03/19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No