Phase 3
Completed N=800
05-001: Treatment of Acute Lymphoblastic Leukemia in Children
Drug/Agent Toxicity by Tissue/Organ · leukemia
Source: ClinicalTrials.gov NCT00400946 ↗
Enrolled (actual)
800
Serious AEs
67.5%
Results posted
Jun 2017
Primary outcomePrimary: Asparaginase-Related Toxicity Rate — 26; 28 percentage of participants — p=.60
◆ Published Evidence
Highly cited
240citations · ~22 / year
Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial.
Summary
RATIONALE: L-asparaginase is an important component of treatment for childhood acute lymphoblastic leukemia, but is also associated with notable side-effects, including hypersensitivity, pancreatitis, and thrombosis. We have previously reported that patients with acute lymphoblastic leukemia in whom asparaginase treatment was discontinued because of intolerable side-effects had survival outcomes that were inferior to those who received all or nearly all of their intended doses. Two bacterial sources of asparaginase exist: Escherichia coli (E coli) and Erwinia chrysanthemia (Erwinia). Generally, the E coli-derived enzyme has been used as front-line therapy and the Erwinia-derived preparation has been reserved for patients who develop hypersensitivity reactions. Pegylated E coli asparaginase (PEG-asparaginase) has a longer half-life and is potentially less immunogenic than native E coli L-asparaginase, and has been used as the initial asparaginase preparation in some pediatric acute lymphoblastic leukemia treatment regimens.
PURPOSE: Although the pharmacokinetics of each of these asparaginase preparations: intravenous PEG-asparaginase (IV-PEG) and intramuscular native E coli L-asparaginase (IM-EC) have been well characterized, their relative efficacy and toxicity have not been studied extensively.
Linked Publications (5)
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Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial.
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Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia.
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Refining risk classification in childhood B acute lymphoblastic leukemia: results of DFCI ALL Consortium Protocol 05-001.
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An investigation of toxicities and survival in Hispanic children and adolescents with ALL: Results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001.
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A lipid-immune network signature defines susceptibility to asparaginase-associated pancreatitis.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Asparaginase-Related Toxicity Rate |
26; 28 | .60 |
| SECONDARY 5-Year Disease-Free Survival |
.89; .90 | — |
| SECONDARY Post-Induction Nadir Serum Asparaginase Activity Level |
0.129; 0.726; 0.143; 0.773; 0.159; 0.787 | — |
| SECONDARY Post-Induction Therapeutic Nadir Serum Asparaginase Activity Rate |
71; 99 | — |
| SECONDARY Induction Infection Toxicity Rate |
26 | — |
| SECONDARY Induction Serum Asparaginase Activity Level |
.694; .505; .211; .048 | — |
| SECONDARY Induction Therapeutic Nadir Serum Asparaginase Activity Rate |
97; 96; 87; 12 | — |
| SECONDARY 5-Year Disease-Free Survival by MRD Day 32 Status |
.79; .90 | — |
| SECONDARY 5-Year Disease-Free Survival by Bone Marrow Day 18 Status |
.89; .78; .88 | — |
| SECONDARY 5-year Disease-Free Survival by CNS Directed Treatment Group |
.89; .89; 1.00; .84; .87 | — |
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of acute lymphoblastic leukemia (ALL)
- No known mature B-cell ALL, defined by the presence of any of the following:
- Surface immunoglobulin
- L3 morphology
- t(8;14)(q24;q32)
- t(8;22)
- t(2;8)
- T-cell surface markers and t(8;14)(q24;q11) allowed
- No secondary ALL
PATIENT CHARACTERISTICS:
- No known HIV positivity
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- No prior therapy except steroids of ≤ 1 week in duration and/or emergent radiation therapy to the mediastinum
- Patients treated with steroids within the past 7 days will not receive steroid prophase during study treatment
Data sourced from ClinicalTrials.gov (NCT00400946) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.