T Cell Lymphoma -Stratified Therapy After Response to First-line Treatment-NR

Inclusion criteria

• At the time of ICF signing, the subject must be 18-70 years of age, inclusive, regardless of gender.
• The subject must have achieved Stable Disease (SD) or Progressive Disease (PD) as assessed per the Lugano 2014 classification criteria after first-line systemic standard therapy (CHOP or a CHOP-like regimen). This includes subjects who failed to achieve a response after at least 4 cycles of standard chemotherapy or who experienced disease progression during treatment.
• The subject must have a histologically confirmed diagnosis of PTCL according to the 2016 revised WHO classification of lymphoid neoplasms (Swerdlow SH et al. 2016). Eligible histological subtypes are restricted to the following: Not Otherwise Specified (PTCL-NOS); ALK-negative Anaplastic Large Cell Lymphoma (ALK- ALCL); Follicular Helper T-cell Lymphoma or PTCL with a TFH phenotype (FTCL or PTCL-TFH). Additionally, they must meet the following condition:

Patients scheduled for allogeneic hematopoietic stem cell transplantation must have a suitable stem cell donor:

i. Related donors must be at least 5/10 matched at HLA-A, -B, -C, -DQB1, and -DRB1.

ii. Unrelated donors must be at least 8/10 matched at HLA-A, -B, -C, -DQB1, and -DRB1.

• Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≤ 2.
• ECOG Performance Status score of 0 or 1, with no deterioration over the preceding two weeks.
• Life expectancy of at least 12 weeks.
• Adequate hepatic, renal, cardiac, and pulmonary function, defined as:

i. Hepatic: Serum total bilirubin ≤ 2 × ULN (or ≤ 3.0 × ULN in cases of Gilbert's syndrome or documented baseline liver involvement); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 × ULN (or ≤ 5.0 × ULN in cases of liver involvement).

ii. Renal: Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft-Gault formula or measured.

iii. Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥ 50% as measured by Multigated Acquisition (MUGA) scan or Echocardiography (ECHO).

iv. Baseline oxygen saturation on room air > 92%. v. Pulmonary: Diffusing capacity of the lungs for carbon monoxide (DLCO), corrected for hemoglobin, ≥ 40% and Forced Expiratory Volume in 1 second (FEV1) ≥ 50% of predicted.

• Voluntary participation in the clinical study; full understanding and awareness of the study and having signed the ICF; willingness and ability to comply with and complete all trial procedures.

Exclusion criteria

• Ann Arbor Stage I disease.
• History of any other malignancy within the past 5 years, except for locally cured malignancies after radical therapy (e.g., basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast).
• Active infection, including:

• Known active or latent tuberculosis, indicated by a positive tuberculin (PPD) skin test (defined as induration >10 mm or per local clinical criteria) or radiographic findings on chest X-ray/CT suggestive of active/latent TB.

• Known history of Human Immunodeficiency Virus (HIV) infection and/or Acquired Immunodeficiency Syndrome (AIDS).

• Chronic active hepatitis B or C infection:

• Hepatitis B virus (HBV) DNA-positive subjects are excluded; those with undetectable HBV-DNA are eligible. The upper limit of normal (ULN) for HBV-DNA is as defined by each participating center.
• Hepatitis C virus (HCV) RNA-positive subjects are excluded; those with undetectable HCV-RNA are eligible. The ULN for HCV-RNA is as defined by each participating center.

• Active viral infections other than hepatitis B or C (e.g., herpes zoster, cytomegalovirus).

• Infection requiring intravenous antimicrobial therapy, evidenced by: hemodynamic instability related to infection, worsening or new infectious symptoms/signs, new infectious foci on imaging, or persistent fever without localizing signs where infection cannot be ruled out.

• Positive serum DNA test for Epstein-Barr virus (EBV).
• Poorly controlled cardiac symptoms or diseases, including:

i. Heart failure > New York Heart Association (NYHA) Class II. ii. Unstable angina. iii. Myocardial infarction within the past year. iv. Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.

• Pregnant or lactating women, and subjects of childbearing potential unwilling to use effective contraception.
• Patients with psychiatric disorders or those unable to provide informed consent.
• PTCL patients with central nervous system involvement.
• PTCL patients who have received prior PD-1/PD-L1 inhibitor therapy.
• Any other condition that, in the investigator's judgment, renders the subject unsuitable for study participation.