Comparison of Duvelisib with Standard Chemotherapy Using Gemcitabine or Bendamustine in Patients with Recurrent or Treatment-Resistant Nodal T-Cell Lymphoma with a TFH Phenotype

Nodal T-cell lymphomas with a TFH phenotype are rare malignant diseases of the lymphatic system that originate from a specific subpopulation of T cells. To date, they have been treated with chemotherapy. The goal of the TERZO study is to investigate the efficacy and safety of duvelisib compared to chemotherapy with gemcitabine or bendamustine. Patients aged 18 and older with nodal T-cell lymphoma with a TFH phenotype are eligible to participate in this study if the disease has returned (recurred) after prior treatment or has not responded adequately to treatment (refractory).

T-cell lymphomas are a type of non-Hodgkin lymphoma and affect T cells, a subgroup of white blood cells that are normally responsible for fighting infections. Nodal T-cell lymphomas with the TFH phenotype (T-follicular helper phenotype) constitute a specific subgroup that includes, among others, angioimmunoblastic T-cell lymphoma (AITL) and follicular T-cell lymphoma (FTCL). In these diseases, abnormal T-cells proliferate uncontrollably, primarily in the lymph nodes. Possible symptoms include swollen lymph nodes, fever, night sweats, weight loss, and general fatigue. Treatment to date has primarily consisted of chemotherapy. However, many patients experience a relapse, or the disease does not respond adequately to therapy. Duvelisib is a so-called dual PI3K inhibitor. The drug specifically blocks the PI3K/AKT/mTOR signaling pathway, which is important for the growth and survival of cancer cells. Duvelisib is taken as a capsule twice daily for 28 days at a time (equivalent to 1 cycle).

The goal of the Phase 3 study is to investigate whether duvelisib prolongs the time during which the disease does not progress (progression-free survival). Duvelisib is being compared to a chemotherapy regimen selected by the study physicians, which has been used in such cases to date. The drugs are either gemcitabine or bendamustine. Gemcitabine is administered as an infusion on days 1, 8, and 15 of a 28-day cycle; bendamustine is administered as an infusion on days 1 and 2 of a 21-day cycle. Both chemotherapy regimens are administered for up to 6 cycles. Patients are randomly assigned to one of the two treatment groups. The study is open-label, which means that both the patients and the study physicians know which treatment is being administered. Other objectives include overall survival, response to therapy, and patients’ quality of life.

Patients with a confirmed diagnosis of nodal T-cell lymphoma with a TFH phenotype and at least one prior systemic treatment are eligible to participate. Patients must not have previously received a PI3K inhibitor. Additionally, they must not have undergone a stem cell transplant in the past. Any prior treatment with gemcitabine or bendamustine must have taken place more than 60 days ago.