Brief Title
Efficacy and Safety of Low-dose Decitabine in Refractory Aplastic Anemia
Official Title
Efficacy and Safety of Low-dose Decitabine in Refractory Aplastic Anemia (LODACA): a Phase 2, Single-arm, Open-label Study
Brief Summary
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Proportion of subjects achieving a hematological response (any of the platelet response, erythroid response, and neutrophil response) after 4 cycles of low-dose decitabine
Secondary Outcome
Incidence of drug-related adverse events
Condition
Refractory Aplastic Anemia
Intervention
Decitabine
Study Arms / Comparison Groups
Decitabine
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
3
Start Date
April 22, 2021
Completion Date
August 9, 2022
Primary Completion Date
July 26, 2022
Eligibility Criteria
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.
Gender
All
Ages
12 Years - N/A
Accepts Healthy Volunteers
No
Contacts
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Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT04854889
Organization ID
IHBDH-DAC202105
Responsible Party
Principal Investigator
Study Sponsor
Institute of Hematology & Blood Diseases Hospital
Study Sponsor
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Verification Date
August 2022