Phase 3
N=218
Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia · Acute Undifferentiated Leukemia · Childhood T Acute Lymphoblastic Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT00557193 ↗Enrolled (actual)
218
Serious AEs
18.4%
Results posted
Dec 2018
Primary outcome: Primary: Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2) — 35.82 percentage probability
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Asparaginase (Drug); Biospecimen Collection (Procedure); Bone Marrow Biopsy (Procedure); Cyclophosphamide (Drug); Cytarabine (Drug); Daunorubicin Hydrochloride (Drug); Dexamethasone (Drug); Echocardiography (Procedure); Etoposide (Drug); Filgrastim (Biological); Laboratory Biomarker Analysis (Other); Lestaurtinib (Drug); Leucovorin Calcium (Drug); Mercaptopurine (Drug); Methotrexate (Drug); Methylprednisolone (Drug); Multigated Acquisition Scan (Procedure); Pegaspargase (Drug); Pharmacological Study (Other); Prednisone (Drug); Therapeutic Hydrocortisone (Drug); Vincristine Sulfate (Drug)
- Age
- Pediatric
- Sex
- All
- Sponsor
- Children's Oncology Group
- Primary completion
- Sep 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2) |
35.82 | — |
| SECONDARY Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2 |
38.89; 35.82 | 0.672 |
| SECONDARY Number of Patients Who Experienced Lestaurtinib-related Dose Limiting Toxicity (DLT) |
0; 1 | — |
| SECONDARY Pharmacokinetic AGP Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy |
— | — |
| SECONDARY Pharmacokinetic Albumin in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy |
— | — |
| SECONDARY Pharmacodynamics PIA Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy |
69.00 | — |
| SECONDARY Describe FLT3 Protein Expression as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts |
1.25; 7.85; 5.83 | — |
| SECONDARY Describe FLT3 Protein Expression as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts |
5.73 | — |
| SECONDARY Describe in Vitro Sensitivity as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts |
0.75; 0.48; 0.47 | — |
| SECONDARY Describe in Vitro Sensitivity as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts |
0.69 | — |
| SECONDARY Percent Probability of Event Free Survival (EFS) by MRD Status and Treatment Arm |
86.05; 87.5; 47.37; 22.73; 51.85; 27.03 | — |
| SECONDARY Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With Survival Outcomes |
— | — |
| SECONDARY Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With PIA Values |
— | — |
| SECONDARY Percent Probability for Event-free Survival (EFS) for Patients on Arm A |
86.67 | — |
Summary
This phase III trial studies combination chemotherapy with or without lestaurtinib with to see how well they work in treating younger patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of stop cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lestaurtinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective with or without lestaurtinib in treating acute lymphoblastic leukemia.
Eligibility Criteria
Inclusion Criteria
- Patients must be enrolled on a Children's Oncology Group (COG) ALL Classification Study (AALL08B1) prior to enrollment on AALL0631
- Patients must be 36 weeks gestational age at the time of diagnosis
- Patients must be newly diagnosed with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL); patients with T-cell ALL are eligible; patients with bilineage or biphenotypic acute leukemia are eligible, provided the morphology and immunophenotype are predominately lymphoid
- Patients must be previously untreated with the exception of steroids and intrathecal chemotherapy; no other systemic chemotherapy may have been administered; patients receiving prior steroid therapy are eligible for study; any amount of steroid pretreatment will not affect initial induction assignment as long as the patient meets all other eligibility criteria; IT chemotherapy per protocol is allowed for patient convenience at the time of the diagnostic bone marrow or venous line placement to avoid second lumbar puncture; (note: the central nervous system [CNS] status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); systemic chemotherapy must begin within 72 hours of this IT therapy
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
- Patients with mature B-cell ALL or acute myelogenous leukemia (AML) are NOT eligible
- Patients with Down syndrome are NOT eligible
Data sourced from ClinicalTrials.gov (NCT00557193). 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.