Aclarubicin Plus Cyclophosphamide, Vincristine, and Prednisone (CAOP) in Patients With Previously Treated Cutaneous T-cell Lymphoma

NCT07535710 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: Acla-CTCL
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Cutaneous T-Cell Lymphoma Refractory; Cutaneous T-Cell Lymphoma, Relapsed; Sezary Syndrome; Cutaneous T Cell Lymphoma (CTCL)

Keywords

Aclarubicin; CTCL; Sezary Syndrome; systemic therapy

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  MTD for aclarubicin (primary outcome measure of phase I)

  28 days after first dose of aclarubicin

• Recommended Phase 2 Dose (RP2D)

  RP2D for aclarubicin (primary outcome measure of phase I)

  28 days after first dose of aclarubicin

• Objective response rate (ORR)

  Proportion of patients who achieved complete remission (CR) or partial remission (PR) after treatment (primary outcome measure of phase II)

  At the end of induction cycle 6 (each cycle is about 28 days)

Secondary Outcomes (6)

• Objective response rate (ORR)

  At the end of induction cycle 6 (each cycle is about 28 days)

• Progression Free Survival

  All enrolled patients were followed up for at least 12 months or had an event

• Time to Next Treatment (TTNT)

  All enrolled patients were followed up for at least 12 months or had an event

• Adverse Events

  From enrollment to 28 days after the end of treatment

• Change in quality of life as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) global health status score

  From enrollment to 28 days after the end of treatment

Study Arms (1)

CAOP

EXPERIMENTAL

Aclarubicin will be used in a dose escalation and dose expansion approach. Cyclophosphamide, Vincristine and Prednisone will be used in a fixed dose throughout the phases. Phase I dose-escalation: a standard "3+3" approach for aclarubicin. Phase II dose expansion: enroll patients same as in phase I, and aclarubicin will be used at the dose determined by the dose escalation. The whole treatment includes induction and maintenance. Induction treatment includes 3 week cycles for 6 cycles of CAOP or until progression. Maintenance treatment includes 6 week cycles for 4 cycles of CAOP or until progression.

Drug: Aclarubicin; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone

Interventions

Aclarubicin DRUG

Cycle 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

CAOP

Cyclophosphamide DRUG

Cycle 1-6 750 mg/m\^2, D1, QD, ivgtt Cycle 7-10 750 mg/m\^2, D1, QD, ivgtt

CAOP

Vincristine DRUG

Cycle 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

CAOP

Prednisone DRUG

Cycle 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

CAOP

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Stage II-B, III, or IV (referring to the Olsen criteria of the International Society for Cancer Research (ISCL)/USCC/EORTC, 2022)
• Patients who have failed at least one systemic therapy; psoralen combined with ultraviolet radiation therapy (PUVA) is not considered a systemic therapy
• All clinically significant toxicities caused by previous anticancer therapy have resolved to ≤ Grade 1 (according to NCI-CTCAE v5.0 criteria)
• Hematological, renal, and liver function tests meet the following requirements:
• Absolute neutrophil count (ANC) ≥ 1,500 cells/μL
• Platelet count ≥ 100,000 cells/μL
• For patients with known bone marrow involvement, ANC ≥ 1,000 cells/μL and platelets ≥ 75,000 cells/μL
• Total bilirubin ≤ 1.5 times the institutional upper limit of normal (ULN) (except for patients with Gilbert syndrome)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; if liver involvement is known in C TCL, ≤ 5.0 × ULN
• Serum creatinine ≤ 1.5 × ULN, or creatinine clearance calculated by the Cockcroft-Gault formula \> 50 mL/min

You may not qualify if:

• 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.
• Patients with significant uncontrolled comorbidities or infections, as follows:
• Uncontrolled infection requiring intravenous antibiotics
• Clinically significant heart disease (New York Heart Association class III or IV), unstable angina
• History of angioplasty, stent implantation, or myocardial infarction within 6 months
• Uncontrolled hypertension despite treatment with two antihypertensive medications (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg, measured on two consecutive occasions, one week apart)
• Clinically significant arrhythmias
• Uncontrolled diabetes mellitus
• Known or tested positive for human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV-1), hepatitis B, or hepatitis C.
• Active herpes simplex or herpes zoster. Patients who have started antiviral prophylaxis ≥30 days prior to the pretreatment visit, have no signs of active infection, and whose last active infection occurred more than 6 months ago may be enrolled and must continue taking prescribed medications during the study.
• Known active autoimmune disease (e.g., Graves' disease, systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, psoriasis).
• Allergic reaction to study medications.

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead
• Leiden University Medical Center: collaborator

Study Sites (2)

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai

Shanghai, China

Location

Ruijin Hospital Wuxi Branch

Wuxi, China

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Recurrence; Sezary Syndrome

Interventions

Aclarubicin; Cyclophosphamide; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Junmin Li, Professor

  Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiong Hu

CONTACT

86-13764313546; hj10709@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician of hematology

Model Details: Phase I Primary Objectives: to evaluate the safety and tolerability of the CAOP regimen in patients with relapsed/refractory cutaneous T-cell lymphoma; to determine the maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs) and to determine the recommended Acla dose for the dose-expansion phase. Phase II Primary Objectives: to evaluate the efficacy of the CAOP regimen in patients with relapsed/refractory cutaneous T-cell lymphoma; the primary endpoint is objective response rate (ORR).

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: April 17, 2026
• Study Start: March 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)