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

A Phase II, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Brentuximab Vedotin Combined With Lisaftoclax in Patients With CD30-positive Cutaneous T-cell Lymphoma

This is a prospective, single-center, open-label, randomized, controlled Phase II clinical trial. The main purpose of this study is to evaluate the efficacy and safety of combining Brentuximab Vedotin (an anti-CD30 antibody-drug conjugate) with Lisaftoclax (APG-2575, a novel BCL-2 inhibitor) in patients with CD30-positive Cutaneous T-Cell Lymphoma (CTCL), specifically including Mycosis Fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL).

Previous studies suggest that the overexpression of the anti-apoptotic protein BCL-2 may contribute to Brentuximab Vedotin resistance in CTCL. Researchers hypothesize that adding a highly selective BCL-2 inhibitor (Lisaftoclax) can reverse this drug resistance, enhance tumor cell apoptosis, and improve clinical outcomes.

In this study, approximately 46 eligible patients will be randomly assigned in a 1:1 ratio to one of two treatment arms:

Monotherapy Arm (Control): Patients will receive Brentuximab Vedotin intravenously at a dose of 1.8 mg/kg every 3 weeks for a total of 16 cycles.

Combination Arm (Experimental): Patients will receive the same Brentuximab Vedotin regimen. Additionally, starting from the 6th cycle, patients will receive oral Lisaftoclax. To mitigate the risk of Tumor Lysis Syndrome (TLS), a daily dose ramp-up will be implemented in the first cycle of Lisaftoclax. Subsequently, Lisaftoclax will be administered at a targeted dose of 600 mg daily on days 1 to 10 of each 21-day cycle, for a total of 9 combination cycles.

The primary endpoint of the study is the Objective Response Rate (ORR) evaluated at the end of the 16 cycles. Secondary endpoints include the improvement of skin lesions (evaluated by mSWAT score), pruritus relief (VAS score), and the incidence of adverse events. Independent, blinded assessors will be utilized to evaluate the clinical responses to reduce bias.

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Cutaneous Anaplastic Large Cell Lymphoma; Cutaneous T-Cell Lymphoma/Mycosis Fungoides
• Intervention / Treatment: Drug: Brentuximab Vedotin (Bv); Drug: Lisaftoclax (APG-2575)

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Peking University First Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Brentuximab Vedotin Monotherapy; Patients will receive Brentuximab Vedotin intravenously at a dose of 1.8 mg/kg every 3 weeks for a total of 16 cycles.	Drug: Brentuximab Vedotin (Bv); Patients will receive Brentuximab Vedotin intravenously at a dose of 1.8 mg/kg every 3 weeks for a total of 16 cycles.
Experimental: Brentuximab Vedotin + Lisaftoclax; Patients will receive Brentuximab Vedotin (1.8 mg/kg, IV, q3w, 16 cycles). Starting from cycle 6, oral Lisaftoclax will be added (600 mg daily on days 1-10 of each 21-day cycle, for 9 cycles, with a daily dose ramp-up in the first cycle).	Drug: Brentuximab Vedotin (Bv); Patients will receive Brentuximab Vedotin intravenously at a dose of 1.8 mg/kg every 3 weeks for a total of 16 cycles.; Drug: Lisaftoclax (APG-2575); Patients will receive Brentuximab Vedotin (1.8 mg/kg, IV, q3w, 16 cycles). Starting from cycle 6, oral Lisaftoclax will be added (600 mg daily on days 1-10 of each 21-day cycle, for 9 cycles, with a daily dose ramp-up in the first cycle).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The percentage of participants who achieve a Complete Response (CR) or Partial Response (PR) at the end of the treatment, evaluated by independent blinded assessors based on clinical skin assessments and radiological imaging.	At the end of 16 treatment cycles (up to approximately 48 weeks)

Collaborators and Investigators

• Sponsor: Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: July 16, 2026
• First Submitted That Met QC Criteria: July 16, 2026
• First Posted (Actual): July 21, 2026

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Hemic and Lymphatic Diseases; Mycosis Fungoides; Lymphoma, Primary Cutaneous Anaplastic Large Cell; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Brentuximab Vedotin; Lisaftoclax
• Other Study ID Numbers: CTCL001; 82425050 (Other Grant/Funding Number: National Natural Science Foundation of China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No