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

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.

Study Overview

• Status: Recruiting
• Conditions: Severe Aplastic Anemia
• Intervention / Treatment: Drug: Cyclophosphamide added to standard immunosuppressive therapy with eltrombopag

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liwei Fang, MD; Phone Number: 13752253515; Email: fangliwei@ihcams.ac.cn
• Study Contact Backup: Name: Hong Pan, MD; Email: panhong@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300131
      • Recruiting
      • Regenerative Medicine Center
      • Contact: Liwei Fang, MD; Phone Number: 13752253515; Email: fangliwei@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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: Experiemental; ALG/CsA(Cyclosporine) + eltrombopag + moderate-dose cyclophosphamide

Drug: Cyclophosphamide added to standard immunosuppressive therapy with eltrombopag; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital
• Investigators: Principal Investigator: Liwei Fang, MD, Institute of Hematology & Blood Diseases Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2023
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: July 27, 2023
• First Submitted That Met QC Criteria: July 27, 2023
• First Posted (Actual): August 4, 2023

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Immunosuppressive Agents
• Other Study ID Numbers: ALG-HPAG-CTX2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No