LODACA: Efficacy and Safety of Low-dose Decitabine in Refractory Aplastic Anemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 [Baseline, 20 weeks, 52 weeks]
Health-related quality of life is measure by the EQ-5D-5L questionnaire.
- 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]
Eligibility Criteria
Criteria
Inclusion criteria:
Subjects eligible for enrollment in the study should meet all of following criteria:
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Diagnosis of acquired aplastic confirmed by peripheral blood and bone-marrow examinations.
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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.
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Persistent decrease of blood cell count, including platelet <30×109/L, and/or hemoglobin <90g/L, and/or absolute neutrophil count <0.5×109/L.
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Age ≥12 years old.
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An Eastern Cooperative Oncology Group performance status score of 0 to 2 at screening.
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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:
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Diagnosis of inherited bone marrow failure disorders.
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Bone marrow reticulin grade of ≥2.
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Having a plan to take thrombopoietin (TPO) receptor agonists.
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Having a plan to undergo hematopoietic stem cell transplantation within 1 year.
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Subjects with hemolytic paroxysmal nocturnal hemoglobinuria clone.
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Having abnormalities of cytogenetic abnormalities related to myelodysplastic syndrome except for +8 or 20q- or -Y.
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Previous or concurrent active malignancies with chemoradiotherapy, except localized tumors diagnosed more than one year previously and treated surgically with curative intent.
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Cytopenias secondary to any other non-hematological disorders (e.g., liver cirrhosis, active connective tissue disease, or chronic persistent infectious diseases).
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Active infection not adequately responding to appropriate therapy.
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Positive for anti-human immunodeficiency virus antibodies, or current infection of hepatitis B virus or hepatitis C virus at screening.
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Concurrent condition of acute hemorrhage in gastrointestinal tract or respiratory tract, or central nervous system.
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Dysfunction of liver: Alanine aminotransferase or aspartate aminotransferase or total bilirubin is more than 2.0 times the upper limit of laboratory normal range.
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Dysfunction of renal: creatinine clear rate is less than 30ml/min.
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Clinically significant dysfunction of heart: class Ⅲ or Ⅳ of the New York Heart Association classification.
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Uncontrolled diabetes mellitus.
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History of congestive heart failure, unstable angina pectoris, myocardial infarction, arterial or venous thrombosis within one year before enrollment.
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Lactating or pregnant women or patients who have no intention of using oral contraceptives or birth control.
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Subjects with psychiatric history or severe cerebrovascular disease with cognitive disorder.
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Participating in other clinical trials within 4 weeks before enrollment.
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Hypersensitivity to decitabine or its components.
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A history of decitabine, azacitidine, or other demethylation agents.
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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).
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Patients who are considered to be ineligible for the study by the investigator for reasons other than above.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Regenerative Medicine Center | Tianjin | Tianjin | China |
Sponsors and Collaborators
- Institute of Hematology & Blood Diseases Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IHBDH-DAC202105