Clinical Study of U29 Injection (CD30-CART) in Patients With CD30-Positive Relapsed/Refractory Lymphoma

A Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of CD30-targeted Chimeric Antigen Receptor T (CAR-T) Cell Injection in Patients With CD30-positive Relapsed or Refractory Lymphoma

This is a single-center, open-label study conducted in subjects with relapsed or refractory CD30-positive lymphoma, with priority given to Hodgkin lymphoma and anaplastic large cell lymphoma.

The primary purpose of this study is to evaluate the preliminary efficacy, safety, and tolerability of CD30-targeted CAR-T cell therapy in participants with CD30-positive relapsed or refractory lymphoma.

Inclusion Criteria:

1. Subjects must provide written informed consent and demonstrate good compliance with study procedures.

2. Age between 18 and 70 years, inclusive; male or female.

3. Histologically confirmed relapsed or refractory lymphoma (with priority for Hodgkin lymphoma, anaplastic large cell lymphoma, or other lymphoproliferative disorders), with CD30 expression confirmed by immunohistochemistry or flow cytometry (≥50% positive cells).

4. Relapsed or refractory disease, defined as:

   • **Hodgkin Lymphoma (HL):**

     1. Failure to achieve remission or disease progression after autologous hematopoietic stem cell transplantation (auto-HSCT); OR

     2. Failure of at least two prior lines of systemic chemotherapy; OR

     3. Ineligibility for auto-HSCT due to:

        1. Chemotherapy resistance (failure to achieve CR or PR after salvage chemotherapy);
        2. Failed stem cell collection, or investigator-assessed inability to collect, or severe comorbidities, or patient refusal of auto-SCT.

   • **Anaplastic Large Cell Lymphoma (ALCL):** Failure of at least two prior lines of systemic chemotherapy or relapse after response.

   • **Other CD30+ lymphomas:** No standard treatment options available, or failure after standard therapy.

5. At least one evaluable lesion according to the Lugano Classification for Malignant Lymphomas (Cheson 2014).

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.

7. Adequate bone marrow reserve at screening:

   • Absolute lymphocyte count (ALC) ≥ 0.3 × 10⁹/L;
   • Platelet count (PLT) ≥ 30 × 10⁹/L (transfusion-supported values are acceptable).

8. Adequate organ function, defined as:

   • Aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN);
   • Alanine aminotransferase (ALT) ≤ 3 × ULN (≤ 5 × ULN if due to tumor infiltration);
   • Total serum bilirubin ≤ 2 × ULN, except for Gilbert's syndrome (total bilirubin ≤ 3 × ULN and direct bilirubin ≤ 1.5 × ULN);
   • Serum creatinine ≤ 1.5 × ULN OR creatinine clearance ≥ 60 mL/min (Cockcroft and Gault formula);
   • No more than grade 1 dyspnea, and oxygen saturation > 91% on room air;
   • Left ventricular ejection fraction (LVEF) ≥ 50% on echocardiogram;
   • International Normalized Ratio (INR) ≤ 1.5 × ULN and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.

9. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to CAR-T infusion. All sexually active males and females of childbearing potential must agree to use effective contraception throughout the study and for at least 1 year after the last dose of study treatment.

10. Adequate venous access for leukapheresis or blood collection, and no contraindications to leukapheresis.

11. Expected survival of at least 3 months.

Exclusion Criteria:

1. History of another malignancy, except for malignancies in complete remission for > 3 years or carcinoma in situ.

2. Lymphoma infiltration of the cardiac atria or ventricles.

3. Use of immunosuppressive agents or corticosteroids within 1 week prior to leukapheresis, unless the investigator determines that the impact on T cells is minimal.

4. Presence of any of the following:

   • Positive hepatitis B e antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab) with HBV-DNA copy number above the lower limit of quantification;
   • Positive hepatitis C antibody (HCV-Ab) with HCV-RNA copy number above the lower limit of quantification;
   • Positive Treponema pallidum antibody (TP-Ab);
   • Positive human immunodeficiency virus (HIV) antibody test.

5. Bacterial, fungal, viral, mycoplasmal, or other type of infection that is judged by the investigator to be difficult to control.

6. Previous or current central nervous system (CNS) disease unrelated to the current lymphoma, such as seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS-related autoimmune disease, unless judged by the investigator to be controllable.

7. Any of the following within 12 months prior to signing informed consent:

   • Cardiac angioplasty or stenting;
   • New York Heart Association (NYHA) Class III-IV congestive heart failure;
   • Myocardial infarction, unstable angina, or other clinically significant cardiac history as judged by the investigator;
   • QTc interval > 480 ms (calculated using the Fridericia formula) at screening;
   • Left ventricular ejection fraction (LVEF) < 50% on echocardiogram.

8. Primary immunodeficiency.

9. History of severe immediate hypersensitivity reaction to any of the study drugs.

10. Administration of a live vaccine within 6 weeks prior to screening.

11. Pregnant or lactating female.

12. Active autoimmune disease.

13. Active acute or chronic graft-versus-host disease (GVHD) at the time of signing informed consent.

14. Allogeneic hematopoietic stem cell transplantation within 6 months prior to signing informed consent.

15. Participation in any other interventional clinical trial within 30 days prior to signing informed consent.

16. Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this study.