Cutaneous T-Cell Lymphoma/Mycosis Fungoides, Primary Cutaneous Anaplastic Large Cell Lymphoma
Conditions
Brief summary
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, ADC) with lisaftoclax (APG-2575, a novel B-cell lymphoma 2 (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 modified severity-weighted assessment tool (mSWAT) score), pruritus relief (visual analog scale (VAS) score), and the incidence of adverse events (AEs). Independent, blinded assessors will be utilized to evaluate the clinical responses to reduce bias.
Interventions
Patients will receive brentuximab vedotin intravenously at a dose of 1.8 mg/kg every 3 weeks for a total of 16 cycles.
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).
Sponsors
Peking University First Hospital
Ascentage Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age greater than or equal to 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 greater than or equal to 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 less than or equal to 2. 6. Adequate hepatic, renal, and hematopoietic function. 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 greater than or equal to 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 B-cell lymphoma 2 (BCL-2) inhibitors. 5. Receipt of corticosteroids for cutaneous T-cell lymphoma (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 greater than or equal to 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 prostate-specific antigen (PSA) levels). 8. Presence of severe organ dysfunction or history of major organ diseases, including: * Cardiac: Left ventricular ejection fraction (LVEF) less than 50%; unstable angina; acute myocardial infarction within the past 6 months; New York Heart Association (NYHA) class III-IV congestive heart failure; clinically significant arrhythmias. * Renal: Creatinine clearance ≤ 50 mL/min. * Hepatic: Aspartate aminotransferase (AST), alanine aminotransferase (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | At the end of 16 treatment cycles (up to approximately 48 weeks) | 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. |
Countries
China
Outcome results
None listed