Cutaneous T-cell lymphomas (CTCL) are a rare and heterogeneous group of extranidal T-cell lymphomas characterized by skin involvement. Current treatment options for CTCL are limited. Although responses have been demonstrated, their duration is often short, especially in patients with advanced stage disease. Additional treatment options are needed which demonstrate activity in cutaneous and extracutaneous sites. The traditional CHOP regimen (Cyclophosphamide, Hydroxydaunorubicin, Vincristine and Prednisone) has some efficacy for CTCL patients, but due to the cardiotoxicity of anthracyclines, patients can only receive a limited course of treatment. After stopping the regimen, most patients will experience relapse.
Aclarubicin, also known as aclacinomycin A, is an anthracycline type of antibiotic with significant anti-cancer properties. Previous studies have shown that aclarubicin only induces histone eviction without causing DNA damage, and it stands out in pre-clinical models and clinical studies, as it potently kills AML cells. Meanwhile, aclarubicin lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. Aclarubicin's treatment indications include malignant lymphoma, but actual clinical application experience is limited.
The purpose of this study is to determine the maximum tolerated dose, safety and efficacy of aclarubicin combined with cyclophosphamide, vincristine, and prednisone (CAOP) for subjects with relapsed or refractory CTCL.
Understand and voluntarily sign the informed consent form
Age ≥ 60 years at enrollment
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Histologically confirmed primary cutaneous T-cell lymphoma (CTCL) or Sézary syndrome (SS) (according to the fifth edition of the WHO Classification of Tumors of the Hematopoietic and Lymphoid System)
Patients diagnosed with a malignancy within the past two years. Exclude the following situation: non-melanoma skin cancer, melanoma in situ, localized prostate cancer (current PSA <0.1 ng/mL), treated thyroid cancer; or cervical carcinoma in situ or breast ductal/lobular carcinoma in situ diagnosed within the past two years, as long as there is no current evidence of active disease.
Clinical evidence of central nervous system (CNS) infiltration.
Large cell transformation (LCT). Patients with a history of LCT but no current invasive disease and no evidence of LCT on skin or lymph node pathology may be enrolled.
Psychiatric illness, disability, or social circumstances that may affect the subject's safety, ability to provide informed consent, or poor compliance.
Single group
Aclarubicin
DrugCycle 1-6: Phase I starting dose 20mg/m\^2/D, D1-2 (dose group 1), D1-3 (dose group 2), D1-4 (dose group 3), QD, ivgtt The Phase II dose was determined based on the Phase I results Cycle 7-10: Phase I starting dose 20mg/ m\^2/D, D1-2 (dose group 1), D1-3 (dose group 2), D1-4 (dose group 3), QD, ivgtt The Phase II dose was determined based on the Phase I results
Cyclophosphamide
DrugCycle 1-6 750 mg/m\^2, D1, QD, ivgtt Cycle 7-10 750 mg/m\^2, D1, QD, ivgtt
Vincristine
DrugCycle 1-6 1.4 mg/m\^2, D1 (maximum 2mg/d), QD, iv Cycle 7-10 1.4 mg/m\^2, D1 (maximum 2mg/d), QD, iv
Prednisone
DrugCycle 1-6 60 mg/m\^2, D1-5 (maximum 100mg/d), QD, Po Cycle 7-10 60 mg/m\^2, D1-5 (maximum 100mg/d), QD, Po
Maximum tolerated dose (MTD)
MTD for aclarubicin (primary outcome measure of phase I)
Recommended Phase 2 Dose (RP2D)
RP2D for aclarubicin (primary outcome measure of phase I)
Objective response rate (ORR)
Proportion of patients who achieved complete remission (CR) or partial remission (PR) after treatment (primary outcome measure of phase II)
Objective response rate (ORR)
Proportion of patients who achieved complete remission (CR) or partial remission (PR) after treatment (secondary outcome measure of phase I)
Progression Free Survival
Time from enrollment to confirmation of disease progression or death from any cause (secondary outcome measure of phase II)
Time to Next Treatment (TTNT)
The interval from commencement of one treatment to initiation of the next line of therapy (secondary outcome measure of phase II)
Adverse Events
Adverse Events (CTCAE v6.0), Vital Signs and Physical Examination, ECOG, Clinical Laboratory Tests, Electrocardiogram (ECG), Echocardiography, Cardiac Enzyme Profile
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Shanghai Jiao Tong University School of Medicine
Lead sponsor
Leiden University Medical Center
Collaborator
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