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

Phase 2

Completed

• Conditions: Response Rate
• Interventions: Drug: Decitabine

• Registration Number: NCT03663751
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-07-01
• Study First Submitted: 2018-09-06
• Study First Submitted QC: 2018-09-06
• Study First Posted: 2018-09-10
• Primary Completion: 2020-12-01
• Study Completion: 2021-03-01
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-19
• Last Update Posted: 2021-05-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Decitabine	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%).

Primary Outcome Measures

Name	Time	Method
Complete response rate	6 months after initiation of treatment	Documentation \>98% donor chimerism of T cells or mononuclear cell in either peripheral blood or bone marrow

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Blood & Marrow Transplantation Center, RuiJin Hospital; 🇨🇳 Shanghai, Shanghai, China