International Study on the Treatment of High-Risk Relapses in Childhood Acute Lymphoblastic Leukemia (ALL), 2010

Acute lymphoblastic leukemia (ALL) is a malignant disease of the hematopoietic system in which immature white blood cells grow uncontrollably and displace healthy blood cells. ALL is the most common form of blood cancer (leukemia) in children. Despite major advances in treatment, relapse remains a serious challenge, especially when it occurs early or in the bone marrow.

The standard treatment for ALL relapse involves intensive chemotherapy consisting of a combination of several anticancer drugs. This study uses the ALL R3 protocol, a combination of six drugs (cytarabine, dexamethasone, methotrexate, pegaspargase, vincristine, and leucovorin). The goal is to achieve remission. This means that the leukemia cells can no longer be detected and normal blood production has resumed. This is often combined with a stem cell transplant. Nevertheless, the chances of a cure are limited in cases of high-risk relapse.

The goal of this Phase 2 study is to investigate the combination of standard chemotherapy with the drug bortezomib to improve the chances of cure for children and adolescents with a high-risk relapse of acute lymphoblastic leukemia (ALL). Patients will be randomly assigned to two groups, and both patients and staff will know which group they are in (open-label study design).

Group 1 receives standard therapy (control arm), and Group 2 receives standard therapy in combination with bortezomib. Bortezomib is a so-called proteasome inhibitor. The proteasome is a structure within the cell responsible for breaking down and recycling old or damaged proteins. By blocking the proteasome, bortezomib causes harmful proteins to accumulate in the cell, leading to programmed cell death of the cancer cells. The drug is already used to treat other types of cancer, but it has not yet been approved for the treatment of relapsed ALL in children and adolescents. Bortezomib is administered intravenously or by subcutaneous injection on Day 1 and Day 4 of Week 1, as well as on Day 1 and Day 4 of Week 3 of chemotherapy. After four weeks, a check is performed to determine whether remission has occurred. The total follow-up period for the study is up to 3 years.

Children and adolescents under the age of 18 who have experienced a first relapse of acute lymphoblastic leukemia (ALL) and are classified as high-risk patients are eligible to participate. They must have written consent from their parents or legal guardians and must not have had ALL with the BCR-ABL genetic mutation, severe neuropathy, or a previous stem cell transplant.