Efficacy and Safety of Low-dose Decitabine in Refractory Aplastic Anemia (LODACA)

Efficacy and Safety of Low-dose Decitabine in Refractory Aplastic Anemia (LODACA): a Phase 2, Single-arm, Open-label Study

This is a phase 2, single-center, single-arm, open-label trial. Simon's two-stage design is performed to evaluate the efficacy of low-dose Decitabine in refractory aplastic anemia.

Study Overview

• Status: Terminated
• Conditions: Refractory Aplastic Anemia
• Intervention / Treatment: Drug: Decitabine

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Regenerative Medicine Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

Subjects eligible for enrollment in the study should meet all of following criteria:

1. Diagnosis of acquired aplastic confirmed by peripheral blood and bone-marrow examinations.
2. Refractory to standard first-line immunosuppressive therapy for at least 6 months, including the combination of rabbit anti-thymocyte globulin (rATG) or porcine anti-lymphocyte globulin (pALG) and cyclosporine (CsA); or ineligible for rATG/ pALG and refractory to CsA alone.
3. Persistent decrease of blood cell count, including platelet <30×10^9/L, and/or hemoglobin <90g/L, and/or absolute neutrophil count <0.5×10^9/L.
4. Age ≥12 years old.
5. An Eastern Cooperative Oncology Group performance status score of 0 to 2 at screening.
6. Patients or their legally authorized representatives who have provided written informed consent of their free will to participate in this study.

Exclusion criteria:

Subjects must be excluded from participating in this study if they meet any of the following criteria:

1. Diagnosis of inherited bone marrow failure disorders.
2. Bone marrow reticulin grade of ≥2.
3. Having a plan to take thrombopoietin (TPO) receptor agonists.
4. Having a plan to undergo hematopoietic stem cell transplantation within 1 year.
5. Subjects with hemolytic paroxysmal nocturnal hemoglobinuria clone.
6. Having abnormalities of cytogenetic abnormalities related to myelodysplastic syndrome except for +8 or 20q- or -Y.
7. Previous or concurrent active malignancies with chemoradiotherapy, except localized tumors diagnosed more than one year previously and treated surgically with curative intent.
8. Cytopenias secondary to any other non-hematological disorders (e.g., liver cirrhosis, active connective tissue disease, or chronic persistent infectious diseases).
9. Active infection not adequately responding to appropriate therapy.
10. Positive for anti-human immunodeficiency virus antibodies, or current infection of hepatitis B virus or hepatitis C virus at screening.
11. Concurrent condition of acute hemorrhage in gastrointestinal tract or respiratory tract, or central nervous system.
12. Dysfunction of liver: Alanine aminotransferase or aspartate aminotransferase or total bilirubin is more than 2.0 times the upper limit of laboratory normal range.
13. Dysfunction of renal: creatinine clear rate is less than 30ml/min.
14. Clinically significant dysfunction of heart: class Ⅲ or Ⅳ of the New York Heart Association classification.
15. Uncontrolled diabetes mellitus.
16. History of congestive heart failure, unstable angina pectoris, myocardial infarction, arterial or venous thrombosis within one year before enrollment.
17. Lactating or pregnant women or patients who have no intention of using oral contraceptives or birth control.
18. Subjects with psychiatric history or severe cerebrovascular disease with cognitive disorder.
19. Participating in other clinical trials within 4 weeks before enrollment.
20. Hypersensitivity to decitabine or its components.
21. A history of decitabine, azacitidine, or other demethylation agents.
22. Receiving TPO-receptor agonists within 1 month before enrollment (other than patients who are treated with TPO-receptor agonists and have no response after at least 4 months treatment).
23. Patients who are considered to be ineligible for the study by the investigator for reasons other than above.

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: Decitabine; Subjects will receive low-dose decitabine for 4 cycles and for another 6 cycles in extension study for patients achieving response during the first 4 cycles.	Drug: Decitabine; Demethylating agents

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects achieving a hematological response (any of the platelet response, erythroid response, and neutrophil response) after 4 cycles of low-dose decitabine	At 20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of drug-related adverse events		Within 52 weeks
Proportion of subjects achieving a hematological response (any of the platelet response, erythroid response, and neutrophil response)		Within 52 weeks
Proportion of subjects with transfusion independence or decreased transfusion requirement		Within 52 weeks
Absolute changes in blood cell count		Within 52 weeks
The utility score of EQ-5D-5L questionnaire	Health-related quality of life is measure by the EQ-5D-5L questionnaire.	Baseline, 20 weeks, 52 weeks
Time from the first decitabine to hematologic response		Within 20 weeks
Duration of hematologic response		Within 52 weeks
Proportion of relapse		Within 52 weeks
Proportion of clonal evolution		Within 52 weeks

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2021
• Primary Completion (Actual): July 26, 2022
• Study Completion (Actual): August 9, 2022

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: April 19, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Hematologic Diseases; Bone Marrow Diseases; Anemia; Hemic and Lymphatic Diseases; Anemia, Aplastic; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Decitabine
• Other Study ID Numbers: IIT2021016

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