Sequential CD19/CD22 CAR-T Cell Therapy Following ASCT

A Clinical Study of Sequential CD19/CD22 CAR-T Cell Therapy Following Autologous Stem Cell Transplantation in Relapsed/Refractory Large B-cell Lymphoma

The goal of this clinical trial is to learn if sequential CD19/CD22 CAR-T cell therapy following autologous stem cell transplantation (ASCT) works to treat relapsed or refractory large B-cell lymphoma (LBCL) in adults. It will also learn about the safety of this treatment combination. The main questions it aims to answer are:

Does ASCT followed by sequential CD19/CD22 CAR-T therapy improve complete response rates in participants with relapsed/refractory LBCL? What medical problems do participants have when receiving this treatment combination? Researchers will evaluate the safety and efficacy of ASCT followed by sequential CD19/CD22 CAR-T therapy to determine if this treatment approach works to improve outcomes for patients with relapsed/refractory LBCL.

Participants will:

Undergo two separate apheresis procedures for stem cell collection and CAR-T cell manufacturing.

Receive conditioning chemotherapy followed by autologous stem cell infusion on day 0.

Receive sequential CD19 and CD22 CAR-T cell infusions over 3 days within one week post-transplant.Visit the clinic regularly for checkups and tests to monitor their response to treatment and any potential side effects.

Keep a record of their symptoms and any adverse events experienced during the treatment period.

Study Overview

• Status: Completed
• Conditions: Auto Stem Cell Transplant; Large B-cell Lymphoma; CAR T Cell Therapy
• Intervention / Treatment: Other: Apheresis and Bridging Therapy; Other: Conditioning and Stem Cell Transplantation; Other: CAR-T Cell Administration

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • The First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy.

   *[Note: LBCL includes: diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS); diffuse large B-cell lymphoma transformed from follicular lymphoma (FL-DLBCL); grade 3b follicular lymphoma (FL); primary mediastinal large B-cell lymphoma (PMBCL); high-grade B-cell lymphoma with rearrangements of MYC and BCL-2 and/or BCL-6 (double-hit/triple-hit lymphoma, DHL/THL)].*

2. Age Restriction: Individuals must be 18 to 70 years old.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
4. Presence of at least one measurable target lesion. *[Note: A target lesion is defined as ≥1 lesion with a longest diameter (LD) >1.5 cm and a longest perpendicular diameter (LPD) ≥1.0 cm, as assessed by computed tomography (CT) or magnetic resonance imaging (MRI).]*

5. Adequate organ function, defined as:

   • Left ventricular ejection fraction (LVEF) ≥50% by echocardiography;
   • Creatinine clearance ≥30 mL/min;
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × upper limit of normal (ULN).

6. Adequate hematopoietic function, defined as:

   • Platelet count ≥45 ×10⁹/L;
   • Hemoglobin ≥8.0 g/dL;
   • Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L.
7. Life expectancy ≥3 months.
8. For women of childbearing potential, a negative pregnancy test is required. Both male and female patients must agree to use effective contraception during treatment and for 1 year thereafter.
9. Willingness to provide written informed consent.

Exclusion Criteria:

1. Prior allogeneic hematopoietic stem cell transplantation or CAR-T cell therapy.
2. Use of immunosuppressive agents or systemic corticosteroids (equivalent to >10 mg prednisone daily) within 2 weeks prior to leukapheresis, or requirement for continued use after enrollment.
3. Active hepatitis B (HBsAg positive with detectable HBV DNA) or hepatitis C (anti-HCV positive with detectable HCV RNA) infection at screening.
4. Uncontrolled active infection requiring intravenous antimicrobial therapy.
5. History of other malignancies within 2 years prior to enrollment (except adequately treated basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ).

6. Significant comorbidities that may compromise study participation or patient safety, including:

   • Severe cardiovascular disease (NYHA Class III/IV heart failure, myocardial infarction within 6 months, unstable arrhythmias, or angina)
   • Severe pulmonary dysfunction (FEV1 or DLCO ≤50% predicted, or requiring supplemental oxygen)
7. HIV infection (positive serology with detectable viral load).
8. Pregnancy, lactation, or unwillingness to use effective contraception.
9. Any condition that in the investigator's judgment would preclude safe participation.

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: ASCT+ CD19/CD22 CAR-T

Other: Apheresis and Bridging Therapy; Patients undergo two separate apheresis procedures: Mobilization and collection of autologous hematopoietic stem cells (HSCs) .; Collection of peripheral blood mononuclear cells (PBMCs) for the manufacture of CD19 and CD22 CAR-T cell products. Bridging therapy may be administered at the investigator's discretion between apheresis and the conditioning regimen.; Other Names: 1; Other: Conditioning and Stem Cell Transplantation; Patients undergo a myeloablative conditioning regimen, followed by the infusion of autologous hematopoietic stem cells on Day 0.; Other Names: 2; Other: CAR-T Cell Administration; Fractionated infusions of CD19-directed and CD22-directed CAR-T cells are completed within one week after HSC infusion.; Other Names: 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Complete Response Rate	Best Complete Response Rate (CRR), defined as the proportion of patients achieving a best response of complete response according to the Lugano 2014 criteria.	From the date of CAR-T cell infusion until the end of the study, with an average follow-up period of approximately 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		From the date of CAR-T cell infusion until the date of death or last follow-up, assessed up to 5 years.
Event-free survival		From the date of CAR-T cell infusion to the date of first event (disease progression, relapse, or death) or last follow-up, assessed up to 5 years.
Adverse event		Within 30 days after CAR-T cell infusion
Best Overall Response Rate	Best Overall Response Rate (ORR), defined as the proportion of patients achieving a best response of complete response (CR) or partial response (PR) according to the Lugano 2014 criteria.	From the date of CAR-T cell infusion until the end of the study, with an average follow-up period of approximately 2 years.

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Actual): September 21, 2023
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: September 26, 2025
• First Submitted That Met QC Criteria: November 15, 2025
• First Posted (Actual): November 19, 2025

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 15, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Surgical Procedures, Operative; Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Stem Cell Transplantation; Blood Component Removal
• Other Study ID Numbers: ASCT+CD19/22 CART

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