TRANSCRIPT: An open label, controlled, randomized multicentric international study evaluating the benefit of autologous stem cell transplantation after complete response in frontline setting patients with T cell-lymphoma

The primary objective of this study is to evaluate whether **autologous stem cell transplantation (ASCT)** is associated with a significant prolongation of progression-free survival (PFS) in patients with **peripheral T-cell lymphoma (PTCL)** who achieve a complete response (CR) following six cycles of induction chemotherapy. This is assessed according to the response criteria for lymphoma, specifically the Lugano 2014 criteria, utilizing PET-CT-based response for FDG-avid lymphomas or CT-based response if not. The clinical relevance of this objective lies in determining the potential benefit of ASCT in improving long-term outcomes for PTCL patients, which could influence treatment protocols and patient management strategies.

Secondary objectives include:

• Comparison of chemotherapy regimens (CHOP/CHOEP/BV-CHP) with and without ASCT consolidation.
• Assessment of overall survival (OS).
• Evaluation of overall response rate (ORR) and complete response rate (CRR) at the end of ASCT, 8-12 weeks post-induction, according to the IWC Lugano 2014 criteria.
• Measurement of duration of response (DoR).
• Conducting a cost-effectiveness analysis (CEA).
• Performing a budget impact analysis (BIA).
• Comparison of central imaging review and local review of metabolic response rate after C4, post-induction, and at the end of ASCT, according to the IWC Lugano 2014 criteria.

The clinical trial involves participants diagnosed with **Peripheral T-cell lymphoma (PTCL)**, specifically those with histologically proven nodal-type PTCL, including subtypes such as PTCL not otherwise specified, follicular helper T-cell lymphomas, and anaplastic large cell lymphoma, ALK-negative. The study population comprises both male and female subjects aged 18 to 69 years, who are fit enough to undergo autologous stem cell transplantation as a consolidation strategy. Participants are required to have a measurable disease by the Lugano criteria and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. The trial includes individuals with a minimum life expectancy of three months and excludes those with stage I disease with normal LDH and PS<2. The sponsor has not provided the total number of participants. Participants must adhere to effective birth control methods if of childbearing potential and be covered by a social security system. The trial population selection criteria ensure that participants can understand and comply with the study requirements, including language proficiency and the ability to attend scheduled visits. The sponsor has not disclosed specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the benefit of **autologous stem cell transplantation** (ASCT) in patients with **peripheral T-cell lymphoma** (PTCL) who achieve a complete response following induction chemotherapy. This study is a randomized, controlled, and multicentric international trial. The trial aims to assess whether ASCT is associated with a significant prolongation of progression-free survival (PFS) in these patients. The trial is expected to run from July 2022 to April 2029, with participants involved for a maximum of six months of treatment, followed by long-term follow-up.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, performance status, and disease characteristics. Eligible participants will then proceed to the treatment phase, which includes six cycles of induction chemotherapy. The chemotherapy regimen involves the administration of drugs such as **etoposide**, **doxorubicin hydrochloride**, **vincristine sulfate**, **cyclophosphamide monohydrate**, **methylprednisolone hemisuccinate**, and **prednisone**, delivered via intravenous infusion or oral use, depending on the specific medication. The maximum treatment period is six months, with doses adjusted according to the protocol's specifications.

Following the treatment phase, participants will have follow-up visits to monitor their response to treatment and any potential side effects. The primary endpoint of the study is modified progression-free survival (mPFS), with secondary endpoints including overall survival (OS), overall response rate (ORR), complete response rate (CRR), and duration of response (DoR). The end-of-study visit will occur after the completion of the follow-up period, where final assessments will be conducted to evaluate the long-term outcomes of the treatment.

Participants are expected to remain in the study for the entire duration unless specific conditions arise that necessitate early termination. These conditions include significant adverse events, withdrawal of consent, or any other protocol-defined criteria. The study is conducted under strict adherence to ethical guidelines, ensuring that all participants provide informed consent and are covered by a social security system. The trial's design and procedures are structured to maintain scientific rigor and ensure the reliability of the results.

The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and routes of administration. **Etoposide Accord Healthcare 20 mg/ml** is provided as a **solution for infusion**. It is administered via **intravenous infusion** with a maximum daily dose of 100 mg/m² and a total dose not exceeding 1800 mg/m² over a treatment period of up to 6 cycles. The active substance, **etoposide**, is of chemical origin.

**Doxorubicin Accord Healthcare 2 mg/ml** is also a **solution for infusion** administered through **intravenous infusion**. The maximum daily dose is 50 mg/m², with a total dose limit of 300 mg/m² over 6 cycles. The active substance, **doxorubicin hydrochloride**, is chemically derived.

**VINCRISIN 1 mg/ml** is provided as an **injection** and administered via **intravenous infusion**. The maximum daily dose is 1.4 mg/m², with a total dose not exceeding 8.4 mg/m² over the treatment period. The active substance, **vincristine sulfate**, is of chemical origin.

**VEPESID 100 mg** is available as a **soft capsule** for **oral use**. The maximum daily dose is 100 mg/m², with a total dose limit of 1800 mg/m² over 6 cycles. The active substance, **etoposide**, is chemically derived.

**Cyclofosfamide Accord 500 mg** is a **solution for injection/infusion** administered via **intravenous infusion**. The maximum daily dose is 750 mg/m², with a total dose not exceeding 4500 mg/m² over the treatment period. The active substance, **cyclophosphamide monohydrate**, is of chemical origin.

**METHYLPREDNISOLONE VIATRIS 40 mg** is provided as a **solution for injection** and administered through **intravenous infusion**. The maximum daily dose is 100 mg, with a total dose limit of 3000 mg over 6 cycles. The active substance, **methylprednisolone hemisuccinate**, is chemically derived.

**CORTANCYL 20 mg** is available as a **tablet** for **oral use**. The maximum daily dose is 100 mg, with a total dose not exceeding 3000 mg over the treatment period. The active substance, **prednisone**, is of chemical origin.

**ADCETRIS 50 mg** is a **solution for infusion** administered via **intravenous infusion**. The maximum daily dose is 1.8 mg/kg, with a total dose limit of 10.8 mg/kg over 6 cycles. The active substance, **brentuximab vedotin**, is a structurally diverse substance classified as an immunoglobulin.

The efficacy of the clinical trial will be assessed primarily through the measurement of **modified progression-free survival (mPFS)** in patients with peripheral T-cell lymphoma (PTCL) who achieve a complete response (CR) following induction chemotherapy. This primary endpoint will be evaluated according to the response criteria for lymphoma as outlined in the Lugano 2014 guidelines. Secondary endpoints include overall survival (OS), overall response rate (ORR), complete response rate (CRR), and duration of response (DoR), all of which will also be assessed using the Lugano 2014 criteria.

The trial will utilize PET-CT-based response assessments for FDG-avid lymphomas, or CT-based assessments if PET-CT is not applicable. These evaluations will be conducted after six cycles of induction chemotherapy to determine the efficacy of autologous stem cell transplantation (ASCT) in prolonging progression-free survival. The study is designed to be open-label, controlled, and randomized, with a multicentric international approach, ensuring a comprehensive evaluation of the treatment's efficacy across diverse patient populations.