A Study of Molecular Subtyping-based Therapeutic Strategies for Cutaneous T-cell Lymphoma (AMITY)

Cutaneous T-cell lymphoma (CTCL) is a group of diseases resulting from clonal hyperplasia of memory T cells in the skin. The increasing incidence and high treatment costs have posed significant challenges to public health and the economy. Current treatment guidelines only provide partial control, leading to varying remission times and recurrence rates. This study aims to use molecular subtyping and immunohistochemistry to guide treatment selection for CTCL patients, aiming to prolong clinical benefit, improve treatment safety, and reduce economic burden.

Study Overview

• Status: Recruiting
• Conditions: Cutaneous T Cell Lymphoma; Cutaneous T-Cell Lymphoma/Mycosis Fungoides
• Intervention / Treatment: Other: molecular subtype based treatment

Detailed Description

The study focuses on the impact of treatment strategy selection based on molecular typing for patients with cutaneous T-cell lymphoma. The study aims to evaluate the effect on clinical benefit time and long-term prognosis, assess the safety of the treatment strategy, and explore the interaction between baseline factors and treatment regimens. This research could potentially provide valuable evidence for precision treatment in the context of cutaneous T-cell lymphoma.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Yang Wang, MD; Phone Number: 86-10-83572350; Email: yangwang_dr@bjmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: WENQING LI, MD; Email: pan-kf@263.net
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Peking University First Hospital
      • Contact: YANG ZHANG, MD; Phone Number: 86-10-83572350; Email: yangwang_dr@bjmu.edu.cn
      • Contact: ZHUOJING CHEN, MD; Phone Number: 86+01083572350; Email: chenzhuojing15@gmail.com
      • Principal Investigator: Yang Wang, MD
      • Sub-Investigator: ZHUOJING CHEN, MD
    • Beijing, Beijing, China, 100191
      • Recruiting
      • Peking University Third Hospital
      • Contact: CHUNLEI ZHANG, MD; Email: zhangchunleius@163.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

In this study, retrospective controls were selected from patients with complete baseline information and previous follow-up information in the cutaneous lymphoma case registry system (TACTICAL database) established in 2009. The prospective study group was a prospective enrollment of patients who met the inclusion criteria, and the immunohistochemistry algorithm established by the previous research group was used to determine the molecular subtype. The corresponding treatment regimen was selected according to the subtype. Follow-up was conducted according to the study design and updated by the ISCL, USCLC, and EORTC (2022) as they evaluate treatment response in patients. The primary outcome was time to clinical benefit (TTNT) of first-line therapy, defined as the time from treatment.

Description

Inclusion Criteria:

• Signed informed consent;
• Patients with CTCL who do not respond well to targeted skin therapy (topical corticosteroids, nitrogen mustard, or phototherapy) in the early stage (stage I-IIA) and advanced stage (stage IIB-IV);
• Age 18-75 years;
• Expected survival time greater than 3 months (follow-up for the historical control group was greater than 3 months);

Exclusion Criteria:

• Received other anti-tumor therapy other than skin-targeted therapy (phototherapy, topical hormones or nitrogen mustard) within the past 1 month prior to enrollment;
• Patients with 2 or more types of primary cutaneous T-cell lymphoma at the same time;
• Combined with other malignant tumors, still receiving anti-tumor therapy;

• Has any other active disease that may increase the risk of protocol therapy or impair the patient's ability to receive protocol therapy, including but not limited to:

  • Comorbid epilepsy;
  • Comorbid autoimmune diseases;
  • Combined with hepatic decompensation;
  • Patients with renal insufficiency and creatinine clearance < 50ml/min;

• Have an uncontrollable medical condition, including but not limited to:

  • Ongoing or active infection;
  • Clinically significant healing or non-healing wounds;
  • Symptomatic congestive heart failure, unstable angina, clinically significant arrhythmias;
  • Significant lung disease (e.g., shortness of breath at rest or light activity, or need for supplemental oxygen for any reason);
  • Diseases/conditions that affect study compliance, such as infectious diseases or psychiatric illnesses/social situations, that are uncontrollable;
• Pregnant (or intending to become pregnant within 2 years) or lactating females;
• Concomitant participation in interventional clinical trials of other clinical trial drugs, except for questionnaire surveys or observational studies;
• Any situation in which the programme is not in compliance;
• Other conditions that in the opinion of the investigator are not suitable for participation in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prospective study group; The group included patients with confirmed cutaneous T-cell lymphoma (CTCL) based on clinical features and histopathology from three research units: Peking University First Hospital, Peking University Third Hospital, and Beijing Institute of Cancer Prevention and Treatment. According to the immunohistochemistry algorithm established previously, the formalin-fixed and paraffin-embedded skin lesions of the patients will be stained. Patients will be assigned to different molecular subtypes, and the treatment strategy will be selected based on the classification.	Other: molecular subtype based treatment; The immunohistochemistry algorithm established by the previous research group was used to determine the molecular subtype, and the corresponding treatment plan was selected according to the subtype. Such as for TCyEM patients, interferon-based immunomodulatory therapy was selected, and TCM-type patients were treated with retinoids.
Retrospective control group; The control group included patients with complete baseline information and previous follow-up data in the TACTICAL database, established by Peking University First Hospital in 2009 for cutaneous lymphoma cases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to next treatment (TTNT)	The time to treatment failure (TTNT) is defined as the duration from the start of treatment to when the treatment is switched to the next systemic therapy or until the patient passes away. Introducing new skin-directed therapy (SDT) alongside topical therapy doesn't indicate treatment failure unless the systemic treatment is changed. If the skin lesion worsens and needs local radiotherapy, it's considered that the systemic therapy has failed. The date of discontinuation of systemic therapy is used when treatment is stopped due to disease progression without further treatment.	From enrollment to the end of treatment at 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR)	The objective response rate (ORR) is defined as the proportion of patients with complete response (CR) and partial response (PR) as per the Primary cutaneous lymphoma: recommendations for clinical trial design and staging update from the ISCL, USCLC, and EORTC (2022). The first CR or PR is achieved and repeated after 4 weeks for confirmation.	From enrollment to the end of treatment at 2 years
time to response (TTR)	Time to response (TTR) is defined as the duration from the start of treatment to the first meeting of CR or PR criteria.	From enrollment to the end of treatment at 2 years
progression-free survival (PFS)	The progression-free survival (PFS) is defined as the period from the beginning of treatment until the first instance of disease progression or death from any cause. Disease progression is defined as advancement to a higher TNMB stage (excluding changes from T1a or T2a to T1b or T2b) or death due to the disease.	From enrollment to the end of treatment at 2 years
overall survival (OS)	The overall survival (OS) is defined as the period from the beginning of treatment to the point of death from any cause.	From enrollment to the end of treatment at 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events and adverse effects	Adverse events and adverse effects: The Preferred Term (PT) for adverse events and the Systemic Organ Classification (SOC) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). For the statistics of adverse event rates, each patient will be counted at most once per SOC and per PT. For the same adverse event that occurs multiple times in the same patient, the severity will be counted according to the severity of multiple occurrences. All adverse events (pre- and intra-treatment adverse events) are included in the list of adverse events	From enrollment to the end of treatment at 2 years

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Collaborators: Peking University Third Hospital; Peking University Cancer Hospital & Institute
• Investigators: Principal Investigator: YANG WANG, MD, Peking University First Hospital

Publications and helpful links

General Publications

• Olsen EA, Whittaker S, Willemze R, Pinter-Brown L, Foss F, Geskin L, Schwartz L, Horwitz S, Guitart J, Zic J, Kim YH, Wood GS, Duvic M, Ai W, Girardi M, Gru A, Guenova E, Hodak E, Hoppe R, Kempf W, Kim E, Lechowicz MJ, Ortiz-Romero P, Papadavid E, Quaglino P, Pittelkow M, Prince HM, Sanches JA, Sugaya M, Vermeer M, Zain J, Knobler R, Stadler R, Bagot M, Scarisbrick J. Primary cutaneous lymphoma: recommendations for clinical trial design and staging update from the ISCL, USCLC, and EORTC. Blood. 2022 Aug 4;140(5):419-437. doi: 10.1182/blood.2021012057.
• Chen Z, Lin Y, Qin Y, Qu H, Zhang Q, Li Y, Wen Y, Sun J, Tu P, Gao P, Wang Y. Prognostic Factors and Survival Outcomes Among Patients With Mycosis Fungoides in China: A 12-Year Review. JAMA Dermatol. 2023 Oct 1;159(10):1059-1067. doi: 10.1001/jamadermatol.2023.2634.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: May 24, 2024
• First Submitted That Met QC Criteria: May 24, 2024
• First Posted (Actual): May 31, 2024

Study Record Updates

• Last Update Posted (Actual): May 31, 2024
• Last Update Submitted That Met QC Criteria: May 24, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Sezary syndrome; cutaneous T-cell lymphoma; mycosis fungoides
• Additional Relevant MeSH Terms: Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Bacterial Infections and Mycoses; Lymphoma; Mycoses; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides
• Other Study ID Numbers: PKU2024162-002; SF2024-1-4074 (Other Grant/Funding Number: Capital's Funds for Health Improvement and Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will only be shared within the participating medical units in the study, including study protocol, informed consent form, clinical study report and statistical analysis plan. Any other institutes requesting for IPD needs to be reviewed by the National Clinical Center for Skin and Immune Diseases in China.

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