Using thiotepa with other drugs for treating relapsed or refractory peripheral T-cell lymphoma

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.

This study is testing a new combination of drugs, including thiotepa, to see if it can help people with relapsed or hard-to-treat peripheral T-cell lymphoma who are getting a stem cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Academic / other)
• Drugs / interventions: chemotherapy, fludarabine
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06468267 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the safety and efficacy of a reduced-intensity conditioning regimen that includes thiotepa, busulfan, fludarabine, and cytarabine for patients undergoing allogeneic hematopoietic stem cell transplantation for relapsed or refractory peripheral T-cell lymphoma. The regimen starts with thiotepa administered on day -7, followed by fludarabine and cytarabine from days -6 to -2, and busulfan from days -4 to -3. Patients will be monitored through bone marrow examinations and FDG-PET/CT imaging post-transplant to assess treatment response and safety. The study aims to provide a new treatment option for patients who have not responded to standard therapies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with relapsed or refractory peripheral T-cell lymphoma who have a suitable stem cell donor.

Not a fit: Patients with ALK+ anaplastic large cell lymphoma or those who are not suitable for or refuse autologous hematopoietic stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with relapsed or refractory peripheral T-cell lymphoma.

How similar studies have performed: Other studies have shown promise with similar conditioning regimens, but this specific combination is being evaluated for the first time in this context.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai General Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Xianmin Song, MD — Shanghai General HospitalShanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Study coordinator: xianmin Song, MD

Conditions Peripheral T Cell Lymphoma; peripheral T cell lymphoma; reduced intensity conditioning regimen; thiotepa