Dose Determination of Brigatinib in Children and Young Adults with ALK-Positive Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumors, or Other Solid Tumors

Anaplastic lymphoma kinase (ALK) is an enzyme that plays an important role in the cell cycle. A change (mutation) in the ALK gene leads to overactivity of the enzyme, which can cause cells to divide uncontrollably and lead to various types of cancer, such as anaplastic large cell lymphoma (ALCL), inflammatory myofibroblastic tumors (IMT), or other solid tumors. In ALCL, T lymphocytes—a type of white blood cell that is part of the immune system—are affected. In IMT, myofibroblasts proliferate uncontrollably. Myofibroblasts possess characteristics of muscle and connective tissue cells and play a role in wound healing, among other functions. If the ALK gene mutation is detectable in the cancer cells, the condition is referred to as ALK-positive. The study drug brigatinib is an inhibitor that specifically targets ALK activity. This targeted therapy is intended to stop the uncontrolled growth of cancer cells. The drug is already approved for the treatment of adults with ALK-positive non-small cell lung cancer (NSCLC) that has recurred after initial treatment. However, for the treatment of children, the drug may currently only be used in clinical trials. In principle, however, drugs that target the ALK mutation are already approved for use in children.

The goal of this Phase 1/2 study is to investigate the efficacy and safety of treatment with brigatinib. To this end, the study is divided into two phases. In Phase 1, patients receive monotherapy with brigatinib, and the goal is to determine a recommended dose. The dose of the drug is increased according to a precise schedule, and its efficacy and the occurrence of side effects are evaluated. In Phase 2, additional patients will be enrolled to receive monotherapy with brigatinib at the previously determined “optimal” dose. In this phase, patients will be divided into groups based on their condition. The study is open-label, meaning that both medical staff and patients know which medication is being administered. Treatments and follow-up examinations as part of the study will continue for up to 2 years, during which the efficacy of the therapy and the occurrence of side effects will be evaluated.

Children and young adults between the ages of 1 and 25 with ALK-positive anaplastic large cell lymphoma, inflammatory myofibroblastic tumors, or other solid tumors that harbor an ALK mutation are eligible to participate in this study. In Phase 2 of the study, only patients with ALK-mutated ALCL or IMT will be enrolled. The disease must have been previously treated and must have shown a recurrence or be uncontrollable (refractory). No prior treatment with brigantinib may have been administered before the start of the study; prior treatment with another ALK inhibitor is permitted.