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

April 14, 2026 updated by: Junmin Li, Shanghai Jiao Tong University School of Medicine

A Multicenter, Open-Label, Phase 1/2 Clinical Study of the Safety and Efficacy of Aclarubicin Plus Cyclophosphamide, Vincristine, and Prednisone (CAOP) in Patients With Previously Treated Cutaneous T-cell Lymphoma

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The estimated incidence of CTCL in China is 6.9 per million, accounting for 75% to 80% of primary cutaneous lymphomas. CTCL has diverse subtypes, stages, and clinical manifestations, with mycosis fungoides (MF) being the most common subtype. The etiology of CTCL remains unclear, but it may be related to DNA damage, epigenetic regulation, programmed cell death, and abnormalities in the T-cell receptor (TCR) signaling pathway.

The diagnosis and classification of CTCL primarily refer to the 5th edition of the World Health Organization (WHO) Classification of Hematopoietic and Lymphoid Neoplasms. A definitive diagnosis requires a comprehensive assessment of the patient's clinical presentation, histopathological findings, immunohistochemical staining, and TCR gene rearrangement testing. Sézary syndrome (SS) is no longer classified as CTCL in 5th edition of the WHO Classification. However, due to its close association with MF, current treatment recommendations still do not separate SS from MF. Early skin manifestations of CTCL include patchy or plaque-like lesions. Advanced stages may develop tumors or erythroderma. Extracutaneous involvement may also occur, often with regional lymph node involvement and the presence of atypical lymphocytes in the peripheral blood. Prognostic factors for CTCL include the presence of extracutaneous involvement, the body surface area of affected skin, the type of skin lesion, and the pathological type. Currently, disease staging and treatment efficacy assessment are primarily based on the 2022 ISCL/USCC/EORTC recommended criteria.

Commonly used systemic therapies for CTCL include interferon α, oral retinoids, histone deacetylase inhibitors, CD30 antibody-drug conjugates (velutuximab), and CCR4 monoclonal antibodies (moglizumab). The global Phase III MAVORIC study of moglizumab demonstrated a median progression-free survival (PFS) of 7.7 months and a median time to next treatment (TTNT) of 11 months in adult patients with relapsed/refractory SS or stage III-IV MF. The objective response rate (ORR) in hematology was 68%, and the ORR in skin reached 42%. However, due to cost and accessibility, clinical application in China remains limited. For patients who have failed these systemic therapies, existing combination chemotherapy regimens, while effective, are limited by patient tolerance, toxicity, and comorbidities, making continued use difficult.

Aclarubicin (Acla) is an anthracycline anticancer drug. In vitro, Acla has demonstrated potent cytotoxicity against various lymphoma and T-lymphocytic leukemia cell lines. Mechanistic studies of anthracyclines have revealed that doxorubicin, epirubicin, daunorubicin, and idarubicin all induce tumor cell apoptosis through two mechanisms: 1. DNA damage: through inhibition of topoisomerase II (Topo II), leading to DNA double-strand breaks (DSBs); and 2. Chromatin damage: through histone removal, causing chromatin alterations at specific genomic loci. However, these dual mechanisms also lead to dose-dependent, irreversible cardiotoxicity. Compared with classic anthracyclines (such as doxorubicin and daunorubicin), Acla does not cause DNA damage and accumulates significantly in lymphoid tissues (spleen, thymus, and lymph nodes), with poor distribution to other tissues. Consequently, its cardiotoxicity is significantly reduced. Even at high cumulative doses, it is less likely to cause cardiac dysfunction. Therefore, Acla may offer a safer option for elderly patients or those with concomitant heart disease. Previous studies have shown that the combination of Acla and cytarabine (such as the CAG regimen) has some efficacy and is well tolerated in relapsed/refractory and elderly patients with acute myeloid leukemia. In the 1980s and 1990s, studies explored the use of Acla in chemotherapy regimens for non-Hodgkin's lymphoma and Hodgkin's lymphoma, demonstrating some activity. Small studies have shown that Acla monotherapy can achieve a response rate of approximately 30% in patients with advanced non-hedging lymphoma, without compromising cardiac function. Japanese researchers have found that combination chemotherapy regimens containing Acla in T-cell lymphomas exhibit superior efficacy.

In this study, the investigators will replace doxorubicin in the traditional CHOP regimen with aclarubicin, a drug with proven efficacy and low cardiotoxicity, to create a novel aclarubicin, cyclophosphamide, vincristine, and prednisone (CAOP) regimen for patients with relapsed/refractory CTCL and SS who have received at least one prior systemic therapy. This combination chemotherapy regimen may improve efficacy while balancing tolerability and safety, providing a new treatment option for elderly patients with CTCL.

Study Type

Interventional

Enrollment (Estimated)

37

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Shanghai, China
        • Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
        • Contact:
      • Wuxi, China
        • Ruijin Hospital Wuxi Branch
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Understand and voluntarily sign the informed consent form
  2. Age ≥ 60 years at enrollment
  3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  4. 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)
  5. Stage II-B, III, or IV (referring to the Olsen criteria of the International Society for Cancer Research (ISCL)/USCC/EORTC, 2022)
  6. Patients who have failed at least one systemic therapy; psoralen combined with ultraviolet radiation therapy (PUVA) is not considered a systemic therapy
  7. All clinically significant toxicities caused by previous anticancer therapy have resolved to ≤ Grade 1 (according to NCI-CTCAE v5.0 criteria)

  8. Hematological, renal, and liver function tests meet the following requirements:

    1. Absolute neutrophil count (ANC) ≥ 1,500 cells/μL
    2. Platelet count ≥ 100,000 cells/μL
    3. For patients with known bone marrow involvement, ANC ≥ 1,000 cells/μL and platelets ≥ 75,000 cells/μL
    4. Total bilirubin ≤ 1.5 times the institutional upper limit of normal (ULN) (except for patients with Gilbert syndrome)
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; if liver involvement is known in C TCL, ≤ 5.0 × ULN
    6. Serum creatinine ≤ 1.5 × ULN, or creatinine clearance calculated by the Cockcroft-Gault formula > 50 mL/min

Exclusion Criteria:

  1. 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.
  2. Clinical evidence of central nervous system (CNS) infiltration.
  3. 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.
  4. Psychiatric illness, disability, or social circumstances that may affect the subject's safety, ability to provide informed consent, or poor compliance.

  5. Patients with significant uncontrolled comorbidities or infections, as follows:

    1. Uncontrolled infection requiring intravenous antibiotics
    2. Clinically significant heart disease (New York Heart Association class III or IV), unstable angina
    3. History of angioplasty, stent implantation, or myocardial infarction within 6 months
    4. 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)
    5. Clinically significant arrhythmias
    6. Uncontrolled diabetes mellitus
  6. Known or tested positive for human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV-1), hepatitis B, or hepatitis C.
  7. 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.
  8. Known active autoimmune disease (e.g., Graves' disease, systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, psoriasis).
  9. Allergic reaction to study medications.
  10. History of allogeneic transplantation.
  11. Pregnancy (confirmed by β-hCG) or lactation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CAOP

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

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

Drug: Cyclophosphamide
Cycle 1-6 750 mg/m^2, D1, QD, ivgtt Cycle 7-10 750 mg/m^2, D1, QD, ivgtt
Drug: Vincristine
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
Drug: Prednisone

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD)
Time Frame: 28 days after first dose of aclarubicin
MTD for aclarubicin (primary outcome measure of phase I)
28 days after first dose of aclarubicin
Recommended Phase 2 Dose (RP2D)
Time Frame: 28 days after first dose of aclarubicin
RP2D for aclarubicin (primary outcome measure of phase I)
28 days after first dose of aclarubicin
Objective response rate (ORR)
Time Frame: At the end of induction cycle 6 (each cycle is about 28 days)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: From enrollment to 28 days after the end of treatment
Adverse Events (CTCAE v6.0), Vital Signs and Physical Examination, ECOG, Clinical Laboratory Tests, Electrocardiogram (ECG), Echocardiography, Cardiac Enzyme Profile
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
Time Frame: From enrollment to 28 days after the end of treatment

Quality of life will be assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).

The global health status score ranges from 0 to 100, with higher scores indicating better quality of life. Scores will be calculated according to the EORTC scoring manual and summarized as change from baseline.
From enrollment to 28 days after the end of treatment
Cancer-related fatigue as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue score
Time Frame: From enrollment to 28 days after the end of treatment

Cancer-related fatigue will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue questionnaire.

Scores are reported as T-scores standardized to a reference population, with higher scores indicating greater fatigue (worse outcome). Changes from baseline will be summarized.
From enrollment to 28 days after the end of treatment
Objective response rate (ORR)
Time Frame: At the end of induction cycle 6 (each cycle is about 28 days)
Proportion of patients who achieved complete remission (CR) or partial remission (PR) after treatment (secondary outcome measure of phase I)
At the end of induction cycle 6 (each cycle is about 28 days)
Progression Free Survival
Time Frame: All enrolled patients were followed up for at least 12 months or had an event
Time from enrollment to confirmation of disease progression or death from any cause (secondary outcome measure of phase II)
All enrolled patients were followed up for at least 12 months or had an event
Time to Next Treatment (TTNT)
Time Frame: All enrolled patients were followed up for at least 12 months or had an event
The interval from commencement of one treatment to initiation of the next line of therapy (secondary outcome measure of phase II)
All enrolled patients were followed up for at least 12 months or had an event

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Jiao Tong University School of Medicine

Collaborators

Leiden University Medical Center

Investigators

  • Principal Investigator: Junmin Li, Professor, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 30, 2026

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

March 20, 2026

First Submitted That Met QC Criteria

April 14, 2026

First Posted (Actual)

April 17, 2026

Study Record Updates

Last Update Posted (Actual)

April 17, 2026

Last Update Submitted That Met QC Criteria

April 14, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Acla-CTCL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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