Efficacy and Safety of Brentuximab Vedotin Combined With Lisaftoclax in CD30+ CTCL (BV-LISA-CTCL)

Inclusion Criteria:

1. Age ≥ 18 years.
2. Confirmed diagnosis of Mycosis Fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL).
3. CD30 positive confirmed by skin biopsy (at least 2 lesion biopsies for MF patients, and at least 1 lesion biopsy for pcALCL patients). CD30 positivity is defined as ≥ 10% of target lymphocytes showing CD30 membrane, cytoplasmic, and/or Golgi-like staining, with a staining intensity higher than the background staining of the corresponding negative control.

4. Prior treatment requirements:

   • pcALCL: Must have received ≥ 1 prior systemic therapy or radiotherapy.
   • MF: Must have received ≥ 1 prior systemic therapy.
   • Note: Patients must be chemotherapy-naïve.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
6. Adequate hepatic, renal, and hematopoietic functions.
7. Females of childbearing potential must be willing to use highly effective methods of contraception during the study and for 6 months after the last dose of study drug; or must be postmenopausal for ≥ 1 year, or surgically sterile.
8. Males, even if surgically sterilized (i.e., post-vasectomy), must agree to use highly effective methods of contraception during the study and for 6 months after the last dose of study drug.
9. No cognitive or communication barriers; capable of understanding and willing to sign a written informed consent form (ICF), and willing to comply with the study visits and procedures.
10. Good venous access for required blood sampling.

Exclusion Criteria:

1. Concomitant diagnosis of systemic Anaplastic Large Cell Lymphoma (sALCL), other Non-Hodgkin Lymphomas (except lymphomatoid papulosis), Sézary syndrome, or stage B2 disease.
2. Active central nervous system (CNS) involvement of lymphoma.
3. Prior treatment with chemotherapy, allogeneic or autologous stem cell transplantation.
4. Prior treatment with Brentuximab Vedotin or any BCL-2 inhibitors.
5. Receipt of corticosteroids for CTCL or skin-directed therapies within 3 weeks prior to the first dose of study drug.
6. Receipt of antibody-directed therapy, immunoglobulin therapy, or other monoclonal antibodies within 12 weeks prior to the first dose of study drug.
7. History of other primary malignancies not in complete remission for ≥ 3 years (exceptions: adequately treated carcinoma in situ of the cervix, non-melanoma skin cancer, squamous intraepithelial lesions, or localized prostate cancer with no evidence of recurrence based on PSA levels).

8. Presence of severe organ dysfunction or history of major organ diseases, including:

   • Cardiac: Left ventricular ejection fraction (LVEF) < 50%; unstable angina; acute myocardial infarction within the past 6 months; NYHA Class III-IV congestive heart failure; clinically significant arrhythmias.
   • Renal: Creatinine clearance ≤ 50 mL/min.
   • Hepatic: AST, ALT, or Alkaline Phosphatase > 3 × Upper Limit of Normal (ULN), or Total Bilirubin > 1.5 × ULN.
9. Active liver or biliary disease (exceptions: Gilbert's syndrome, asymptomatic gallstones, liver involvement by lymphoma, or stable chronic liver disease assessed by the investigator).
10. History of severe cerebrovascular disease within the past 6 months, or current presence of symptomatic/sequelae cerebrovascular events.
11. History of pancreatitis or high-risk factors for pancreatitis.
12. Uncontrolled systemic bacterial, fungal, viral, or other severe infections.
13. Positive test for Human Immunodeficiency Virus (HIV) or Hepatitis B virus (positive HBsAg or HBcAb).
14. Known hypersensitivity to recombinant proteins, murine proteins, or any excipients of the study drugs.
15. Female patients who are pregnant, lactating, or planning to become pregnant within 6 months.
16. Presence of severe concurrent medical/psychiatric conditions that may compromise patient safety or compliance, or interfere with informed consent, study participation, or interpretation of results.
17. Any other conditions that, in the opinion of the investigator, make the patient unsuitable for study participation.