Why are we doing this research?
The purpose of this study is to test the good and bad effects of the study drugs bortezomib and vorinostat when they are given in combination with chemotherapy commonly used to treat acute lymphoblastic leukemia (ALL) in infants. For example, adding these drugs could decrease the number of leukemia cells, but it could also cause additional side effects. Bortezomib and vorinostat have been approved by the US Food and Drug Administration (FDA) to treat other cancers in adults, but they have not been approved for treating children with leukemia.
- Treatment will consist of 4 main phases: Remission Induction, Consolidation, Reinduction, and Maintenance. High risk patients will receive a reintensification phase prior to transplant in first remission.
- REMISSION INDUCTION: Chemotherapy will be given in an attempt to induce the participant's leukemia into remission. Drugs given are intrathecal triple drug treatment with methotrexate, hydrocortisone and Ara-C (ITMHA); dexamethasone; vorinostat; bortezomib; PEG-asparaginase; mitoxantrone; cyclophosphamide; cytarabine; and 6-mercaptopurine.
- CONSOLIDATION PHASE: After the participant's blood counts have recovered from Remission Induction, he/she will move to the consolidation phase. This therapy is given to kill any remaining leukemia cells. Drugs given are ITMHA, high-dose methotrexate, and 6-mercaptopurine.
- RE-INDUCTION: This phase aims to improve the participant's overall response to therapy by again seeking to bring his/her leukemia into remission. Drugs given are ITMHA, mitoxantrone, peg-asparaginase, dexamethasone, bortezomib, and vorinostat.
- RE-INTENSIFICATION: If the participant's maximum residual disease (MRD) is not negative after consolidation, he/she will receive intensification therapy, then go on to stem cell transplant (SCT) (SCT not part of this study).
- MAINTENANCE PHASE: Participants with negative MRD after consolidation will skip the re-intensification phase and proceed to receive maintenance therapy to keep the leukemia from returning. Drugs given are ITMHA, dexamethasone, vincristine, 6-mercaptopurine and methotrexate. Each cycle of these drugs lasts 28 days and will be repeated up to 20 times as long as there are no serious side effects.
Study Type: Interventional
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Who can participate?
AGES ELIGIBLE FOR STUDY: up to 365 Days (Child)
- Patient is ≤ 365 days of age at the time of diagnosis.
- Patient has newly diagnosed acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia with ≥25% blasts in the bone marrow (M3), with or without extramedullary disease. Patients with T-cell ALL are eligible. Patients with bilineage or biphenotypic acute leukemia are eligible, provided the morphology and immunophenotype are predominantly lymphoid.
- Limited prior therapy, including systemic glucocorticoids for one week or less, one dose of vincristine, and one dose of intrathecal chemotherapy.
- Written informed consent following Institutional Review Board, NCI, FDA, and Office for Human Research Protections (OHRP) Guidelines.
- Patients with prior therapy, other than therapy specified in the Inclusion Criteria.
- Patients with mature B-cell ALL or acute myelogenous (AML).
- Patients with Down syndrome.
- Inability or unwillingness of legal guardian/representative to give written informed consent.