Cyclophosphamide Added to Standard Immunosuppressive Therapy With Eltrombopag as Front-line Therapy in Patients With Severe Aplastic Anemia

Study Overview
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Brief Summary
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This is a prospective, single-center, single-arm, phase 2 study. The aim of this study is to evaluate the efficacy and safety of Anti-lymphocyte globulin plus eltrombopag in combination with moderate-dose cyclophosphamide for severe aplastic anemia.

Official Title
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Cyclophosphamide Added to Standard Immunosuppressive Therapy With Eltrombopag as Front-line Therapy in Patients With Severe Aplastic Anemia

Conditions
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Severe Aplastic Anemia

Intervention / Treatment
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* Drug: Cyclophosphamide added to standard immunosuppressive therapy with eltrombopag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age ≥ 12 years Subject has a diagnosis of naïve severe or very severe aplastic anemia ECOG performance status ≤2 Unwilling or unable to receive allogeneic hematopoietic stem cell transplantation. Willing and able to comply with the requirements for this study and written informed consent. Exclusion Criteria: Previously received immunosuppressive therapy > 4 weeks Previously treated with TPO-RA > 4 weeks Have an allergy or intolerance to either eltrombopag or cyclophosphamide. Have an allergy to ALG Uncontrolled systemic fungal, bacterial, or viral infection Poorly controlled hypertension (≥140/90mmHg) or diabetes (a fasting plasma glucose concentration ≥7.0mmol/L or a random venous plasma glucose concentration ≥11.1mmol/L) Abnormal liver or kidney function: ALT or AST >3 ULN, or serum creatinine (sCr)≥ 2.5 ULN. History of radiotherapy and chemotherapy for malignant solid tumors Combined with other serious disorders Pregnant or breast-feeding patients Patients considered to be ineligible for the study by the investigator for reasons other than the above.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experiemental<br>ALG/CsA(Cyclosporine) + eltrombopag + moderate-dose cyclophosphamide | Drug: Cyclophosphamide added to standard immunosuppressive therapy with eltrombopag<br>* Severe aplastic anemia patients will receive a daily dose of Anti-lymphocyte globulin (25mg/kg) for the initial five days at the beginning of the treatment. Cyclosporine will be administered daily at a dosage of 3-5mg/kg. Eltrombopag will be administered daily at a dosage of 15mg starting from the first day of treatment and continuing for a duration of six months. The moderate-dose cyclophosphamide (20mg/kg) will be administered on days 29-30 and days 43-44.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Percentage of patients with hematological response. Hematological response includes complete rate, near complete rate(CR), very good partial response(VGPR), Meaningful partial response(mPR) and partial response(PR). | Within 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Robust response | Percentage of patients with robust response, including CR, near CR, VGPR and mPR. | Within 3 months | 
| All-cause mortality |  | Within 3 months | 
| Time to achieve robust hematological response |  | Within 6 months | 
| Incidence of the adverse event | Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event | Within 6 months |