Low-dose Decitabine for the Treatment of Decreased Donor Chimerism After Allogeneic Stem Cell Transplantation

Study Overview
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Brief Summary
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Decreasing donor chimerism is considered as an early sign of graft failure or relapse in patients undergoing allogeneic stem cell transplantation. The treatment option included tapering or stop of immunosuppression and or donor lymphocyte infusion (DLI) which may restore a full donor chimerism but subsequent graft versus host disease (GVHD) is the major complications. In this single arm prospective study, the investigator evaluate the effect and safety of low-dose decitabine alone or with DLI in patients with decreased donor chimerism after allo-HSCT.

Detailed Description
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Decreasing donor chimerism is considered as an early sign of graft failure or relapse in patients undergoing allogeneic stem cell transplantation. The treatment option included tapering or stop of immunosuppression and or donor lymphocyte infusion (DLI) which may restore a full donor chimerism but subsequent GVHD is the major complications. In this single arm prospective study, the investigator plan to evaluate the effect and safety of low-dose decitabine treatment alone in patients with decreased donor chimerism after allo-HSCT. The investigators expect an overall response rate of 80% without serious toxicity such as grade III-IV aGVHD, ext cGVHD and lethal infection event associated with low-dose decitabine (LD-DAC) treatment. In case of donor chimerism decreasing, 5-day low-dose decitabine (5mg/m2) will given every 6 to 8 weeks until full donor chimerism is achieved (>98%). Fast withdraw of immuno-suppression or stop of immunosupression is not carried out in the study.

Official Title
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Pre-emptive Therapy With Low-dose Decitabine for Patients With Decreased Donor Chimerism After Allogeneic Stem Cell Transplantation

Conditions
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Response Rate

Intervention / Treatment
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* Drug: Decitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: all patients after allogeneic stem cell transplantation decreasing of donor chimerism to less than 97% providing inform consent Exclusion Criteria: patients with documented relapse disease patients with documented positive MRD+ (>0.1% via flowcytometry or PCR) patients with active infection or grade III-IV GVHD

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 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: Treatment<br>The peripheral and bone marrow T cell and mono nucleated cell chimerism will be closely followed-up. In case of decreasing donor chimerism, patients will receive low-dose decitabine with 5mg/m2 daily for 5 days every 6-8 weeks until the chimerism recovered to full donor type (>98%). | Drug: Decitabine<br>* low-dose decitabine: 5mg/m2 daily for 5 days<br>* Other names: LD-DAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate | Documentation >98% donor chimerism of T cells or mononuclear cell in either peripheral blood or bone marrow | 6 months after initiation of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse rate | Documentation of blast in bone marrow >5% | 12 months after initiation of treatment | 
| engraftment failure | Documentation of pancytopenia with donor chimerism <5% | 12 months after initiation of treatment | 
| survival rate | event counted as death due to any cause | 12 months after initiation of treatment | 
| incidence of grade III-IV aGVHD | event counted as documentation of new onset or aggravation of pre-existing aGVHD into grade III-IV | 12 months after initiation of treatment | 
| incidence of moderate to severe chronic GVHD | event counted as documentation of moderate to severe chronic GVHD | 12 months after initiation of treatment | 
| Overall response | Documentation of complete or partial response | 6 months after initiation of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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donor chimerism,, decitabine,, allo-HSCT