Reduced Dose of Cyclophosphamide Combined With Standard Immunosuppressive Therapy to Treat Severe Aplastic Anemia (hypo-CASH)

Reduced Dose of Cyclophosphamide Combined With Standard Immunosuppressive Therapy as Front-line Therapy in Patients With Severe Aplastic Anemia

This is a prospective, single-center, single-arm, phase 2 study. This study aims to evaluate the efficacy and safety of anti-lymphocyte globulin plus herombopag in combination with the reduced dose of cyclophosphamide (hypo-CASH) for severe aplastic anemia.

Study Overview

• Status: Recruiting
• Conditions: Severe Aplastic Anemia; Cyclophosphamide Reduced-dose; Immunosuppressive Therapy
• Intervention / Treatment: Drug: Reduced dose of cyclophosphamide combined with standard immunosuppressive therapy

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jingyu Zhao, MPH; Phone Number: 13752253515; Email: zhaojingyu@ihcams.ac.cn
• Study Contact Backup: Name: Hong Pan, MD; Phone Number: ‭15822458611‬; Email: panhong@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 301617
      • Recruiting
      • Red Blood Cell Disorders Center and Regenerative Medicine Center
      • Contact: Hong Pan, MD; Phone Number: ‭15822458611‬; Email: panhong@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subject has a diagnosis of naïve severe or very severe aplastic anemia
• Male or female age ≥ 12 years
• Unwilling or unable to receive allogeneic hematopoietic stem cell transplantation.
• ECOG performance status ≤2
• 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 anti-lymphocyte globulin, cyclosporine, herombopag or cyclophosphamide.
• Uncontrolled fungal, bacterial, or viral infection. Hepatitis-associated aplastic anemia is allowed; hepatitis B or C infection is permitted unless it causes severe liver failure.
• Tested positive for HIV or syphilis
• Presence of severe liver, kidney, or heart failure, or other life-threatening comorbidities.
• History of radiotherapy and chemotherapy for malignant solid tumors in recent 5 years
• 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: hypo-CASH; ALG/CsA and herombopag and reduced dose of cyclophosphamide

Drug: Reduced dose of cyclophosphamide combined with standard immunosuppressive therapy; 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. Herombopag will be administered daily at a dosage of 15mg starting from the first day of treatment and continuing for a duration of six months. Cyclophosphamide (20mg/kg) will be administered on days 15-16.

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), good partial response(GPR) and partial response(PR).	Within 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of the adverse event	Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event	Within 6 months
Superior response rate	Percentage of patients with superior response, including CR, VGPR and GPR.	With in 6 months
Overall response rate	Percentage of patients with hematological response. Hematological response includes complete rate, near complete rate(CR), very good partial response(VGPR), good partial response(GPR) and partial response(PR).	With in 6 months
Time to achieve robust superior response		Within 6 months
First time to response		Within 6 months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: November 16, 2024
• First Submitted That Met QC Criteria: November 16, 2024
• First Posted (Estimated): November 19, 2024

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 16, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Hematologic Diseases; Bone Marrow Diseases; Anemia; Anemia, Aplastic; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Immunosuppressive Agents
• Other Study ID Numbers: Hypo-CASH-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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