RIC With Thiotepa Combined With Bu/Flu/Ara-C in Allo-HSCT for Relapsed or Refractory PTCL.

NCT ID: NCT06468267

Last Updated: 2024-08-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-15
• Study Completion Date: 2026-07-15

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.

Conditions

Peripheral T Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intervention arm

Participants will receive allogenetic hematopoietic stem cell transplantation (allo-HSCT) with the reduced intensity conditioning regimen including thiotepa(5mg / kg / d-7d ( 1d )), fludarabine (30mg / m2 / d, -6d--2d ( 5d )), Ara-C (1g / m2 / d, -6d--2d ( 5d )), and busulfan(3.2mg / kg / d, -4d-3d ( 2d )).

Group Type: EXPERIMENTAL

Thiotepa

Intervention Type: DRUG

The reduced intensity conditioning regimen is composed by thiotepa (5mg / kg / d-7d (1d)), fludarabine (30mg / m2 / d, -6d--2d (5d)), Ara-C (1g / m2 / d, -6d--2d (5d)), and busulfan (3.2mg / kg / d, -4d-3d (2d)).

Interventions

Thiotepa

The reduced intensity conditioning regimen is composed by thiotepa (5mg / kg / d-7d (1d)), fludarabine (30mg / m2 / d, -6d--2d (5d)), Ara-C (1g / m2 / d, -6d--2d (5d)), and busulfan (3.2mg / kg / d, -4d-3d (2d)).

Intervention Type: DRUG

Other Intervention Names

fludarabine; busulfan; Cytarabine

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xianmin Song, MD

OTHER

Sponsor Role: lead

Responsible Party

Xianmin Song, MD

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Xianmin Song, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai General HospitalShanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Locations

Shanghai General Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

xianmin Song, MD

Role: CONTACT

shongxm@139.com

+86 1350167250

Facility Contacts

Xianmin Song, MD

Role: primary

shongxm@139.com

+86 21 63240090 ext. 3175

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Other Identifiers

SHSYXY-202402-THI-FAB

Identifier Type: -

Identifier Source: org_study_id