Congenital Dyserythropoietic Anemia (CDA)
Conditions
Keywords
Congenital Dyserythropoietic Anemia, Zoledronic Acid
Brief summary
Background: Congenital Dyserythropoietic Anemia (CDA) is a group of rare hereditary blood disorders characterized by ineffective erythropoiesis, leading to chronic anemia and organ damage. Current treatment options are very limited, mainly relying on regular blood transfusions, which can cause severe complications over time. Our laboratory research and animal models suggest that Zoledronic acid, a medication commonly used for bone health, may improve ineffective erythropoiesis. Purpose: The purpose of this exploratory study is to evaluate the efficacy and safety of Zoledronic acid in adult patients with CDA who do not have other effective treatment options. The primary goal is to see if this treatment can increase hemoglobin levels and reduce the need for blood transfusions. Study Design: This is a prospective, single-center, single-arm study. Participants will receive an initial intravenous dose (4 mg) of Zoledronic acid. After a 4-week observation period to ensure safety, participants will receive additional doses every 4 weeks for a total of 4 doses. Researchers will monitor hemoglobin levels, transfusion frequency, spleen size, and overall quality of life over a period of 12 to 24 weeks.
Interventions
DRUGzoledronic acid
Zoledronic acid will be administered at a dose of 4 mg via a standardized intravenous (IV) infusion lasting no less than 15 minutes. To ensure safety, the initial dose is followed by a 4-week rigorous observation period. If the treatment is well-tolerated without significant adverse events, subsequent doses will be given every 28 days for a total of 4 cycles. Patients will be closely monitored for serum calcium levels and renal function (eGFR) throughout the intervention period to mitigate potential risks associated with bisphosphonate therapy.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years, regardless of gender. * Diagnosis of Congenital Dyserythropoietic Anemia (CDA) based on clinical presentation, laboratory tests, and family investigation, with the presence of RBM28 mutation and/or increased vacuolization within nucleated red blood cells under light microscopy of bone marrow. * Presence of anemia (Hemoglobin \< 100 g/L at screening) or transfusion dependence (defined as an average transfusion interval of \< 8 weeks within the past 3 months). * Performance status is acceptable (ECOG score 0-2). * Normal renal function (estimated glomerular filtration rate, eGFR ≥ 60 mL/min/1.73m²). * Serum calcium levels within the normal range. * Female patients of childbearing potential must have a negative pregnancy test before enrollment and agree to use effective contraception during the study and for 3 months after completion. * The patient and/or guardian voluntarily sign the informed consent form.
Exclusion criteria
* Known hypersensitivity to bisphosphonates or any of their excipients. * Severe periodontal disease or a recent history (within 6 months) of osteonecrosis of the jaw. * Hypocalcemia. * Pregnant or lactating women. * Currently receiving other experimental drug treatments that may affect erythropoiesis (e.g., Luspatercept). * Active, uncontrolled systemic infection. * Severe cardiac, pulmonary, or hepatic dysfunction, as judged by the investigator to be unsuitable for participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin Level From Baseline | 12 weeks after the first dose | The primary endpoint is the hematologic response achieved by participants at 12 weeks after the first dose of Zoledronic acid. Response includes: 1) Complete Response (CR): Hemoglobin ≥ 120 g/L; 2) Partial Response (PR): Not meeting CR criteria, but achieving independence from red blood cell transfusions OR an increase in HGB of ≥ 20 g/L from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin Level at 4 Weeks | 4 weeks after the first dose | Assessment of the increase in peripheral blood hemoglobin concentration from baseline to 4 weeks after the first dose |
| Change in Red Blood Cell Transfusion Interval | Up to 24 weeks | Comparison of the time interval between red blood cell transfusions before and after Zoledronic acid treatment |
| Change in Spleen Size | Up to 24 weeks | Assessment of the change in spleen size measured by ultrasound compared to baseline |
| Change in Quality of Life Assessed by the 36-Item Short Form Health Survey (SF-36) | Up to 24 weeks | Assessment of the change in patient quality of life compared to baseline. It is measured using the 36-Item Short Form Health Survey (SF-36). The score ranges from 0 to 100, where a higher score indicates a better quality of life. |
Countries
China
Contacts
CONTACTXin Zhao, MD
Outcome results
None listed