Clinical trial NCT06468267: RIC With Thiotepa Combined With Bu/Flu/Ara-C in Allo-HSCT for Relapsed or Refractory PTCL.
Official title: Reduced Intensity Conditioning With Thiotepa Combined With Busulfan, Fludarabine and Cytarabine in Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Relapsed or Refractory Peripheral T-cell Lymphoma.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Peripheral T Cell Lymphoma
Keywords: peripheral T cell lymphoma
reduced intensity conditioning regimen
thiotepa
Lead sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2024-06-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a single-center, single-arm, prospective phase II clinical trial that evaluates the efficacy and safety of an reduced-intensity conditioning (RIC) regimen with thiotepa combined with busulfan, fludarabine, and cytarabine for allogeneic hematopoietic stem cell transplantation in the treatment of relapse and refratory peripheral T-cells lymphoma. The conditioning regimen includes thiotepa at a dose of 5mg/kg/d at d -7 (1 day), fludarabine at 30mg/m2/d from d -6 to d -2 (5 days), cytarabine at 1g/m2/d from d -6 to d -2 (5 days), and busulfan at 3.2mg/kg/d from d -4 to d -3 (2 days). Conditioning begins on day -7, and donor hematopoietic stem cell infusion is performed on day 0. All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year after transplantation. FDG-PET/CT imaging will be adopted every 6 months after transplantation. If disease relapse is suspected during the follow-up period, bone marrow and relapse site examinations will be conducted at any time. The primary study endpoints are the 1-year and 2-year progression-free survival (PFS) rates post-transplant. Secondary study endpoints include the incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative relapse rates at 1 year and 2 years post-transplant, 1-year and 2-year overall survival (OS), graft-versus-host disease-free, relapse-free survival (GRFS), non-relapse mortality (NRM), cumulative incidence of chronic GVHD, and the incidence of Cytomegalovirus （CMV）and Epstein-Barr virus（EBV）reactivation within 1 year.


Eligibility criteria: Inclusion Criteria:

* Age between 18 and less than 70 years, regardless of gender
* Peripheral T-cell lymphoma (PTCL) was diagnosed according to the 2016 WHO criteria and met any of the following criteria: Relapse: Except ALK+ anaplastic large cell lymphoma （ALCL), CR was achieved by standard chemotherapy but disease progressed，and relapse after hematopoietic stem cell transplantation;Refractory: Except ALK+ anaplastic large cell lymphoma （ALCL), the tumor shrank \< 50% or progressive disease after 4 courses of standard chemotherapy, or not achieve CR after 6 courses of standard chemotherapy;Not suitable for or refusing autologous hematopoietic stem cell transplantation.
* Patients must have a suitable hematopoietic stem cell donor:Related donors must have at least 5/10 matches for HLA-A, -B, -C, -DQB1, and - DRB1;Unrelated donors must have at least 8/10 matches for HLA-A, -B, -C, -DQB1, and -DRB1
* Hematopoietic cell transplantation comorbidity index (HCT-CI) score ≤ 2
* ECOG (Eastern Cooperative Oncology Group) performance status: 0-2
* Adequate liver, kidney, and cardiopulmonary function, meeting the following requirements:Serum creatinine ≤ 1.5x ULN (the upper limit of normal);Cardiac function: Ejection fraction ≥ 50%;Baseline oxygen saturation \> 92%;Total bilirubin ≤ 2.0 x ULN; ALT and AST ≤ 2.0 x ULN，AKP ≤ 2.0 x ULN;Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40% and FEV1 (Forced Expiratory Volume in 1 second) ≥ 50%
* Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form

Exclusion Criteria:

* PTCL patients did not meet the criteria of relapse / refractory.
* Refuse to adopt allegeneic hematopoietic stem cell transplantation.
* History of malignancies other than lymphoid tumors within the 5 years prior to screening, except for adequately treated in situ cervical cancer, basal cell carcinoma, squamous cell carcinoma of the skin, and curatively treated localized prostate cancer or ductal carcinoma in situ
* ECOG ≥ 3.
* HCT-CI score ≥ 3.
* Any unstable systemic diseases, including but not limited to unstable angina, recent cerebrovascular accidents or transient ischemic attacks within the 3 months prior to screening, myocardial infarction within the 3 months prior to screening, congestive heart failure (New York Heart Association \[NYHA\] class ≥ III), severe arrhythmias requiring drug treatment after pacemaker implantation, significant liver, kidney, or metabolic diseases, and pulmonary arterial hypertension.
* Active, uncontrolled infections, including those associated with hemodynamic instability, new or worsening infection symptoms or signs, new infectious lesions on imaging, or persistent unexplained fever without signs or symptoms of infection.
* HIV-infected individuals.
* Active hepatitis B (HBV) or active hepatitis C (HCV) requiring antiviral therapy.
* History of autoimmune diseases
* Pregnant or breastfeeding women.
* Fertile males and females unwilling to use contraception during the treatment period and for 12 months after treatment.

Primary outcomes:
measure: 1y and 2y-progression-free survival (PFS)
timeFrame: up to 1 years for the 1y-PFS and up to 2 years for the 2y-PFS
Secondary outcomes:
measure: acute graft-versus-host disease (aGVHD)
timeFrame: up to 180 days
measure: 1y and 2y-cumulative relapse rates (CIR)
timeFrame: up to 1 years for the 1y-CIR and up to 2 years for the 2y-CIR
measure: 1y and 2y-overall survival (OS)
timeFrame: up to 1 years for the 1y-OS and up to 2 years for the 2y-OS
measure: graft-versus-host disease-free, relapse-free survival (GRFS)
timeFrame: up to 2 years
measure: non-relapse mortality (NRM)
timeFrame: up to 2 years
measure: cumulative incidence of chronic GVHD
timeFrame: up to 2 years
measure: CMV and EBV reactivation
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
Study officials:
affiliation: Shanghai General HospitalShanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: Xianmin Song, MD
role: PRINCIPAL_INVESTIGATOR
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