Multi-omics Profiling of Patients With Aplastic Anemia Before and After CD7-CAR-T Therapy

NCT07139600 | Active Not Recruiting

• 1 other identifier: XYFY2024-KL365-01
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Aplastic anemia (AA) is a life-threatening bone marrow failure disorder characterized by pancytopenia and hypocellular bone marrow, with immune-mediated destruction of hematopoietic stem and progenitor cells (HSPCs) playing a central role in its pathogenesis. Although immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT) have improved survival, a significant proportion of patients remain refractory, relapse after treatment, or lack suitable donors for transplantation. Therefore, novel therapeutic strategies are urgently needed. Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy in hematologic malignancies. CD7 is an early surface marker of T-lineage cells and is dispensable for T cell development and function, making it a promising therapeutic target. This exploratory study aims to investigate the molecular and cellular mechanisms of CD7-CAR-T therapy in AA patients by analyzing multi-omics changes before and after treatment. This is a prospective, single-center, single-arm, open-label study enrolling patients with relapsed or refractory severe aplastic anemia. Participants will receive autologous CD7-CAR-T cells following lymphodepletion. Multi-omics profiling, including genomics, transcriptomics, proteomics, and immunophenotyping, will be performed on patient samples before and after infusion. The primary objective is to explore dynamic molecular changes associated with treatment response and disease progression. Secondary objectives include safety evaluation and preliminary assessment of efficacy. Findings from this study may provide mechanistic insights into CD7-CAR-T therapy in AA and inform the development of innovative immunotherapies for bone marrow failure syndromes.

Conditions

Aplastic Anaemia; CAR-T; CD7 Positive

Outcome Measures

Primary Outcomes (4)

• Objective Response Rate (ORR)

  The proportion of patients achieving Complete Response (CR) or Partial Response (PR)

  Up to 36 months post-infusion.

• Progression-Free Survival (PFS)

  Time from CAR-T cell infusion to disease progression, relapse, or death from any cause, whichever occurs first.

  Up to 36 months post-infusion.

• Overall Survival (OS)

  Time from CAR-T cell infusion to death from any cause.

  Up to 36 months post-infusion.

• Event-Free Survival (EFS)

  Time from CAR-T cell infusion to the occurrence of any of the following events: failure to achieve response, disease progression or relapse, initiation of alternative therapy, or death from any cause.

  Up to 36 months post-infusion.

Secondary Outcomes (1)

• Safety and Tolerability

  From infusion through study completion (up to 36 months).

Interventions

CD7 CAR-T cells infusion BIOLOGICAL

Autologous T cells are collected by leukapheresis, activated, and transduced with a retroviral vector encoding a CD7-specific CAR. Following fludarabine/cyclophosphamide lymphodepletion, CD7-CAR-T cells (3 × 10\^6/kg) are infused intravenously. This intervention is distinguished by its CD7 target, aiming to suppress aberrant T-cell-mediated marrow destruction and restore hematopoiesis in aplastic anemia.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients (≥18 years) with refractory or relapsed severe aplastic anemia (SAA) after standard immunosuppressive therapy, or ineligible for/allogeneic hematopoietic stem cell transplantation. Participants must have ECOG 0-1, life expectancy ≥3 months, suitable venous access for leukapheresis, and meet basic lab criteria. Key exclusions include active infections, severe cardiovascular disease, recent malignancy, pregnancy/breastfeeding, or known HIV, HBV, or HCV infection.

You may qualify if:

• Age ≥18 years at the time of informed consent, of Chinese nationality. ECOG performance status 0-1, with an expected survival time ≥3 months.
• Diagnosis of severe aplastic anemia (SAA) and meeting at least one of the following:
• Relapsed or refractory after standard therapy without achieving complete remission.
• Ineligible for, without access to, or refusing allogeneic hematopoietic stem cell transplantation.
• Laboratory values at screening meeting all of the following:
• Serum creatinine ≤2.5 × upper limit of normal (ULN). Oxygen saturation ≥90% at baseline. Total bilirubin ≤3 × ULN. ALT and AST ≤3 × ULN. Adequate venous access for mononuclear cell collection and no contraindications to leukapheresis.
• Female participants of childbearing potential must have a negative high-sensitivity serum pregnancy test (β-hCG) at screening and before the first dose of fludarabine/cyclophosphamide. Male and female participants of childbearing potential must agree to use effective contraception from informed consent through at least 36 months after CD7-CAR-T infusion.
• After review by the investigator team, the overall benefit of trial participation is judged to outweigh potential risks.
• Ability to understand and sign informed consent, and willingness to comply with study procedures and restrictions.

You may not qualify if:

• History of or treatment for other malignancies within 5 years prior to screening, except adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer, curatively treated localized prostate cancer, or ductal carcinoma in situ.
• Severe systemic diseases, including:
• NYHA class III or IV congestive heart failure. Stroke, myocardial infarction, or hemodynamically unstable arrhythmia within 6 months prior to consent.
• Left ventricular ejection fraction (LVEF) \<50% by echocardiography. Severe or uncontrolled concomitant illness within 14 days prior to consent, including active infection.
• Pregnant or breastfeeding women. Positive serology for HIV. Positive for hepatitis B surface antigen or detectable HBV DNA. Positive for hepatitis C antibody with detectable HCV RNA. Positive syphilis serology (TP-Ab and RPR). Positive CMV DNA.
• History of life-threatening hypersensitivity to CD7-CAR-T cells or any excipients (including DMSO), or known hypersensitivity to biologics such as antibodies or cytokines.
• Contraindications to fludarabine or cyclophosphamide therapy. History of alcohol dependence, substance abuse, or psychiatric disorders that may interfere with study compliance.
• Any other condition that, in the opinion of the investigator, makes the participant unsuitable for the study.

Sponsors & Collaborators

• Xuzhou Medical University: lead

Study Sites (1)

Xuzhou Medical University

Xuzhou, Jiangsu, 221006, China

Location

MeSH Terms

Conditions

Anemia, Aplastic

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• Hai Cheng

  The Affiliated Hospital oh Xuzhou Medical University

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Hematologist of The Affiliated Hospital of Xuzhou Medical University

Study Record Dates

• First Submitted: August 17, 2025
• First Posted: August 24, 2025
• Study Start: August 1, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)