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

Обзор

This study is a multicenter, two-arm, prospective clinical trial, comprising two groups: the allogeneic hematopoietic stem cell transplantation group (Allo-HSCT) and the alternative salvage regimens. It aims to evaluate the efficacy and safety of Allo-HSCT and alternative salvage regimens in the treatment of peripheral T-cell lymphoma that has achieved no response (NR) after first-line therapy. During the screening/baseline period, informed consent will be obtained, and inclusion/exclusion criteria will be verified. Group assignment (Allo-HSCT vs. alternative salvage regimens) will be determined taking into account the availability of a matched donor and the patient's preference. The study plans to enroll 29 patients in each group. Data on demographics and medical history will be collected, and assessments including vital signs, physical examination, PET-CT, bone marrow aspiration smear, flow cytometry, and bone marrow pathology will be performed.

Вмешательства

• Процедура Allogenic stem cell transplant (ASCT)
  ASCT involves the infusion of stem cells collected from a donor (genetically similar, but not identical).
• Процедура Salvage Therapy
  This term encompasses a range of potential alternative regimens instead of allogeneic hematopoietic stem cell transplantation

Первичные конечные точки

• 2y-overall survival (OS) [Срок оценки: up to 2 years for the 2y-OS]

Вторичные конечные точки (2)

• 2y-progression-free survival (PFS) [Срок оценки: up to 2 years for the 2y-PFS]
• non-relapse mortality (NRM) [Срок оценки: up to 1 year]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• Shanghai General Hospital — Шанхай

Публикации

• Tournilhac O, Altmann B, Friedrichs B, Bouabdallah K, Leclerc M, Cartron G, Turlure P, Reimer P, Wagner-Drouet E, Sanhes L, Houot R, Roussel M, Kroschinsky F, Dreger P, Viardot A, de Leval L, Rosenwald A, Gaulard P, Wulf G, Villate A, Latiere C, Elmaagacli A, Glass B, Poeschel V, Damaj G, Sibon D, Durot E, Bilger K, Banos A, Haenel M, Dreyling M, Keller U, Tiab M, Drenou B, Cornillon J, Nguyen S, PMID 39270145
• Schmitz N, Truemper L, Bouabdallah K, Ziepert M, Leclerc M, Cartron G, Jaccard A, Reimer P, Wagner E, Wilhelm M, Sanhes L, Lamy T, de Leval L, Rosenwald A, Roussel M, Kroschinsky F, Lindemann W, Dreger P, Viardot A, Milpied N, Gisselbrecht C, Wulf G, Gyan E, Gaulard P, Bay JO, Glass B, Poeschel V, Damaj G, Sibon D, Delmer A, Bilger K, Banos A, Haenel M, Dreyling M, Metzner B, Keller U, Braulke F, PMID 33512419

Идентификаторы

NCT: NCT07470996 · SHSYXYK-PTCL-NR-Prospective

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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