Total Therapy Study XVI for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Status:
Active, not recruiting
Trial end date:
2022-03-01
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 3
Details
Lead Sponsor:
St. Jude Children's Research Hospital
Collaborators:
Enzon Pharmaceuticals, Inc. National Cancer Institute (NCI) National Institute of General Medical Sciences (NIGMS)