New combination therapy with belinostat or pralatrexate combined with chemotherapy for newly diagnosed peripheral T-cell lymphoma

Peripheral T-cell lymphoma (PTCL) is a rare and aggressive form of non-Hodgkin lymphoma. It originates in T cells, a subtype of white blood cells that are normally responsible for fighting infections. In this disease, abnormal T cells multiply uncontrollably and can settle in lymph nodes, bone marrow, or other organs. The exact causes of PTCL have not yet been fully elucidated. Genetic changes and a disruption in immune regulation are suspected. The currently recommended standard treatment consists of what is known as CHOP chemotherapy, a combination of the active ingredients cyclophosphamide, doxorubicin, vincristine, and prednisone. Although this treatment is initially effective for many patients, relapses are common, making new therapeutic approaches urgently needed. The CRESCENDO study is testing two additional active ingredients. Belinostat is a so-called histone deacetylase inhibitor. It alters gene activity in cancer cells and can thus slow or stop tumor growth. Pralatrexate belongs to the class of folic acid analogs and specifically inhibits cell division in rapidly growing cells. This drug is already approved for use when the disease is active again, but not for untreated patients.

The goal of the CRESCENDO study is to evaluate the efficacy and tolerability of these two drugs in combination with standard chemotherapy and to compare them with standard therapy alone. The study is divided into two phases. In Part 1, small groups of patients will first be studied to determine which dosage of the two active ingredients is best tolerated. In this phase, patients will receive either belinostat in combination with CHOP or pralatrexate in combination with COP (a variant of CHOP without doxorubicin). In Part 2 of the study, the effectiveness of these two combinations will then be compared with that of the standard treatment. To this end, participants will be randomly assigned to one of three treatment groups: belinostat + CHOP, pralatrexate + COP, or CHOP alone. Each patient will receive up to six treatment cycles at three-week intervals. This will be followed by regular follow-up care, including physical examinations and diagnostic imaging. This follow-up care is designed to monitor the course of the disease over several years.

Certain eligibility criteria must be met to participate in the study. Patients must be at least 18 years old. Patients with the following conditions are excluded from participation: precursor T-cell lymphoma or leukemia, adult T-cell leukemia/lymphoma, T-cell prolymphocytic leukemia, T-cell leukemia with large granular lymphocytes, primary cutaneous anaplastic large-cell lymphoma (ALCL), cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome), as well as ALCL, provided that treatment with brentuximab vedotin is possible. The condition must not have been previously treated, and at least one tumor lesion must be measurable. Previous treatment with belinostat or pralatrexate excludes participation. Pregnant or breastfeeding individuals are also excluded from participation.