A Study Using Subject-specific MRD to Adopt Treatment After HSCT for Subjects With MDS

A Phase II Multicenter Single-armed Study Using Subject-specific Minimal Residual Disease Markers to Adopt Treatment After Allogeneic Stem Cell Transplantation for Subjects With Myelodysplastic Syndrome

The goal of this interventional study is to evaluate if pre-emptive intervention using Azacitidine and / or donor lymphocytes or tapering of immune suppression in measurable residual disease (MRD) positive subjects can prevent clinical relapse. Participants will undergo MRD surveillance and be subjected to intervention in case of MRD positivity. Results will be compared with NMDSG14B, part one, in which MRD was analyzed in included patients without recieving intervention.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Acute Myeloid Leukemia With Myelodysplasia Related Disease and < 30% Blasts; Mixed Myelodysplastic/Myeloproliferative Disease
• Intervention / Treatment: Drug: Azacitidine; Other: Donor lymphocytes; Other: Tapering of immune suppression

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Magnus Tobiasson, PhD; Phone Number: 0046858580000; Email: magnus.tobiasson@ki.se

Study Locations

• Sweden
  • Stockholm, Sweden
    • Recruiting
    • Department of Hematology, Karolinska University Hospital
    • Contact: Magnus Tobiasson, PhD
    • Principal Investigator: Andreas Björklund

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Signed informed consent

• Age ≥ 18 years
• Subjects eligible for SCT
• Subjects having the disease MDS, mixed myelodysplastic/myeloproliferative syndrome or AML with myelodysplasia related dysplasia and 20-29% marrow blasts
• All female subjects of childbearing potential have to have negative pregnancy test within 2 weeks prior to inclusion to the study

Exclusion Criteria:

• No traceable genetic aberration identified either in screening next generation sequencing panel or next generation sequencing panel performed at diagnosis
• Uncontrolled hypertension, heart, liver, kidney related or other uncontrolled medical or psychiatric disorders
• Mental inability, reluctance or language difficulties that results in difficulty understanding the meaning of study participation

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
Experimental: Intervention in MRD positive patients; Azacitidine and / or Donor lymphocytes or tapering of immune suppression	Drug: Azacitidine; Azacitidine; Other: Donor lymphocytes; Donor lymphocytes in patients without immune suppression; Other: Tapering of immune suppression; Tapering of immune suppression in patients who are on immune suppressive drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical event defined as relapse or death within 1 year from first MRD+ sample	Within 1 year from first MRD+ sample

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of MRD+ patients achieving MRD negativity	From MRD positivity until 2y after transplantation
Incidence and severity of graft-versus host disease	From transplantation until 2y after transplantation
Safety, adverse events reporting	After start of Azacitidine until 30 days after last azacitidine injection
Relapse-free survival	From transplantation until 2y after transplantation
Overall survival	From transplantation until 2y after transplantation

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: Nordic MDS Group
• Investigators: Principal Investigator: Magnus Tobiasson, PhD, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: March 27, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Preleukemia; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: NMDSG14B, part 2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes