Study on the drug inotuzumab ozogamicin (InO) in children with a first relapse of acute lymphoblastic leukemia (ALL)

Acute lymphoblastic leukemia (ALL) is a malignant disease of the hematopoietic system characterized by the uncontrolled production of immature white blood cells (blasts) in the bone marrow. ALL affects lymphocytes, a subtype of white blood cells. A common form of ALL, which occurs particularly frequently in children, is B-cell progenitor ALL (BCP-ALL). The overproduction of blasts disrupts normal blood formation and the immune system. In ALL, other organs or the central nervous system may also be affected. Consequently, fatigue, anemia, blood clotting disorders, fever, and an increased susceptibility to infections may occur. As part of the diagnostic process, tests are conducted to determine, among other things, which surface proteins are expressed on the cancer cells (e.g., the CD22 protein). These tests are used to determine the disease’s risk profile.

Standard treatment for ALL is divided into several phases (induction, consolidation, maintenance). The goal of induction therapy is to achieve complete remission (complete regression of the disease). However, the disease may recur during treatment. A standard chemotherapy regimen is also available for this situation, which is administered, for example, according to the so-called ALLR3 protocol—a defined regimen consisting of several drugs. Inotuzumab ozogamicin is an antibody-drug conjugate that specifically binds to the CD22 protein on cancer cells, penetrates the cancer cell, and releases a toxic agent (calicheamicin) inside the cell. The drug is effective in adults and is therefore already approved for the treatment of relapsed/refractory BCP-ALL in adults. Its efficacy in children has not yet been studied.

The goal of this Phase 2 study is to investigate the efficacy and safety of treatment with inotuzumab ozogamicin in children with a first relapse compared to standard therapy (ALLR3 protocol). As part of the study, patients will be randomly assigned to two groups in a 2:1 ratio. Group 1 (2/3 of the patients) will receive the study drug inotuzumab ozogamicin (infusions on days 1, 8, and 15 of a 28-day cycle). Group 2 (1/3 of the patients) will receive the standard ALLR3 chemotherapy (mitoxantrone, vincristine, dexamethasone, and PEG-asparaginase). The study is open-label, meaning that medical staff and patients (or their parents) know which medications are being administered. After completion of induction therapy, standard consolidation and maintenance therapy will be initiated in both groups. Treatments and follow-up examinations as part of the study will continue for up to 5 years, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. The primary endpoint of the study is achieving minimal residual disease (MRD) negativity after induction therapy. MRD indicates how many cancer cells can still be detected in the blood or bone marrow using specialized testing methods. The fewer there are, the better the prognosis.

Patients between the ages of 1 and 17 with BCP-ALL are eligible to participate in this study. The disease must be a first relapse, classified as high-risk, and CD22-positive. The ALL must be Philadelphia chromosome-negative, and no stem cell transplant may have been performed to date.