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

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

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.

Study Overview

• Status: Completed
• Conditions: Response Rate
• Intervention / Treatment: Drug: Decitabine

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Blood & Marrow Transplantation Center, RuiJin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: Treatment; 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; low-dose decitabine: 5mg/m2 daily for 5 days; Other Names: LD-DAC

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Jiong HU, Department of Hematology, Rui Jin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: September 6, 2018
• First Posted (Actual): September 10, 2018

Study Record Updates

• Last Update Posted (Actual): May 21, 2021
• Last Update Submitted That Met QC Criteria: May 19, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: allo-HSCT; donor chimerism,; decitabine,
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: RJ-BMT-2018-1

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