Acute Lymphoblastic Leukemia | Total Therapy Study XVI for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia research study
What is the primary objective of this study?
The primary objective of this study (TOTXVI) is to compare the clinical benefit, the pharmacokinetics, and the pharmacodynamics of polyethylene glycol-conjugated (PEG) asparaginase given in higher dose (HD PEG) versus those of PEG-asparaginase given in conventional dose (CD PEG) during the continuation phase. This study has several secondary objectives: Therapeutic Objectives: To estimate the event-free survival and overall survival of children with ALL who are treated with risk-directed therapy. To study whether intensifying induction, including fractionated cyclophosphamide and thioguanine, in patients with day 15 MRD > 5%, will result in improved leukemia cytoreduction in this subgroup compared to TOTXV. To assess whether intensification of central nervous system (CNS)-directed intrathecal and systemic chemotherapy will improve outcome in patients at high risk of CNS relapse. Exploratory Pharmacologic Objectives: To identify pharmacogenetic, pharmacokinetic and pharmacodynamic predictors for treatment-related outcomes in the context of the systemic therapy used in the protocol. To compare the pharmacokinetics and pharmacodynamics of PEG-asparaginase given in higher dose (3,500 or 3,000 units/m2) versus those of PEG-asparaginase given in conventional dose (2,500 units/m2) in the continuation phase. Exploratory Biologic Objectives: To determine the prognostic value of levels of minimal residual disease in peripheral blood at day 8 of remission induction. To validate new markers and methods for MRD detection. To genotype natural killer (NK) cell receptors and measure their expressions at diagnosis and before reinduction, and to associate these features with treatment outcome. To identify new prognostic factors by applying new technologies to study patient material (e.g., stored plasma, serum, cerebrospinal fluid, and normal and leukemic cells). Exploratory Neuroimaging Objectives: To use quantitative MR measures (Diffusion Tensor Imaging and high resolution volumetric imaging) to assess differences in myelin and cortical thickness development in patients treated for ALL relative to healthy controls matched for age and gender. To assess the impact of folate pathway genetic polymorphisms on myelin and cortical thickness development and neurocognitive performance. To assess the impact of frontal-parietal lobe myelin and cortical thickness development on neurocognitive performance in attention, working memory, fluency, visual-spatial reasoning and processing speed.
Who is eligible to participate?
Inclusion Criteria: - Participant has a confirmed diagnosis of precursor B-cell or precursor T-cell acute lymphocytic leukemia (ALL) by immunophenotyping - Participant is less than or equal to 18 years of age - Limited prior therapy, including systemic glucocorticoids for one week or less, one dose of vincristine, emergency radiation therapy to the mediastinum and one dose of intrathecal chemotherapy. Other circumstances must be cleared by principal investigator (PI) or co-PI. - Written, informed consent and assent following Institutional Review Board, NCI, FDA, and Office for Human Research Protections (OHRP) Guidelines. Exclusion Criteria: - Participants with prior therapy, other than that listed above - Pregnant or lactating - Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Acute Lymphoblastic Leukemia
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Prednisone, Vincristine, Daunorubicin, PEG-L-asparaginase, Erwinia L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, ThioguanineSee Detailed Description section for details of treatment interventions.
Drug:Clofarabine, Methotrexate, Mercaptopurine, Dexamethasone, Etoposide, DasatinibSee Detailed Description section for details of treatment interventions.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
HD PEGParticipants randomized to receive higher dose PEG-asparaginase during the continuation phase. Interventions: Prednisone, Vincristine, Daunorubicin, PEG-L-asparaginase, Erwinia L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Thioguanine Clofarabine, Methotrexate, Mercaptopurine, Dexamethasone, Etoposide, Dasatinib
CD PEGParticipants randomized to receive conventional dose PEG-asparaginase during the continuation phase.. Interventions: Prednisone, Vincristine, Daunorubicin, PEG-L-asparaginase, Erwinia L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Thioguanine Clofarabine, Methotrexate, Mercaptopurine, Dexamethasone, Etoposide, Dasatinib
Active, not recruiting
Start Date: October 29, 2007
Completed Date: November 30, 2020
Phase: Phase 3
Primary Outcome: Continuous complete remission of patients receiving high-dose and conventional dose PEG-asparaginase.
Secondary Outcome: Event-free survival
Study sponsors, principal investigator, and references
Principal Investigator: Sima Jeha, MD
Lead Sponsor: St. Jude Children's Research Hospital
Collaborator: National Cancer Institute (NCI)