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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Myelodysplastic Syndromes, Acute Myeloid Leukemia With Myelodysplasia Related Disease and < 30% Blasts, Mixed Myelodysplastic/Myeloproliferative Disease

Intervention / Treatment
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* Drug: Azacitidine
* Other: Donor lymphocytes
* Other: Tapering of immune suppression


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Intervention in MRD positive patients<br>Azacitidine and / or Donor lymphocytes or tapering of immune suppression | Drug: Azacitidine<br>* Azacitidine<br>Other: Donor lymphocytes<br>* Donor lymphocytes in patients without immune suppression<br>Other: Tapering of immune suppression<br>* Tapering of immune suppression in patients who are on immune suppressive drugs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |