New Combination Therapy for Children and Young Adults with Relapsed or Treatment-Resistant Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma with Alterations in the JAK-STAT Signaling Pathway

Acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) are forms of blood cancer that occur most frequently in children and adolescents and originate from immature white blood cells (lymphoblasts). While ALL primarily affects the blood and bone marrow, LBL often presents as a tumor in lymph nodes or organs. With modern therapies, both diseases have good chances of cure—most children can be cured in the long term. In difficult cases, such as a relapse or when the disease does not respond to treatment (refractory), the prognosis is poorer. Therefore, new therapies are being sought to improve the chances of a cure. In some patients, the cancer cells exhibit changes in specific genes—the so-called IL-7R/JAK-STAT signaling pathway. This signaling pathway controls cell growth and survival and can be used as a target for new therapies. The study treatment combines five active ingredients: Ruxolitinib is a JAK inhibitor that specifically blocks the JAK-STAT signaling pathway in cancer cells. Venetoclax is a BCL-2 inhibitor that triggers the natural death of cancer cells. Dexamethasone is a corticosteroid (a cortisone-like drug) with anti-inflammatory and anticancer effects. Cyclophosphamide and cytarabine are chemotherapy drugs that inhibit the proliferation of cancer cells.

The goal of this Phase 1/2 study is to investigate the efficacy and safety of the combination therapy consisting of ruxolitinib and venetoclax, together with dexamethasone, cyclophosphamide, and cytarabine. In Phase 1 of the study, the optimal dosage of the combination therapy will be determined, and in Phase 2, this treatment will be administered to a larger study group. In addition to the combination therapy, all patients will receive age-adjusted intrathecal chemotherapy (administration of medications into the cerebrospinal fluid) to counteract the disease’s spread to the central nervous system. The study is open-label, meaning that both medical staff and patients know which medications are being administered. The primary endpoint of the study is the maximum tolerable dose of medication without unacceptable side effects (Phase 1) and the overall response rate to the therapy (Phase 2).

Children, adolescents, and young adults aged 1 to 21 years with relapsed or refractory acute lymphoblastic leukemia or lymphoblastic lymphoma are eligible to participate in this study. The initial diagnosis of the disease must have been made before the age of 19, and alterations in the IL-7R and/or JAK-STAT signaling pathways must have been detected.