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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00557193




Registration number
NCT00557193
Ethics application status
Date submitted
9/11/2007
Date registered
12/11/2007
Date last updated
9/04/2019

Titles & IDs
Public title
Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Scientific title
A Phase III Study of Risk Directed Therapy for Infants With Acute Lymphoblastic Leukemia (ALL): Randomization of Highest Risk Infants to Intensive Chemotherapy +/- FLT3 Inhibition (CEP-701, Lestaurtinib; NSC#617807)
Secondary ID [1] 0 0
NCI-2009-00313
Secondary ID [2] 0 0
AALL0631
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia 0 0
Acute Undifferentiated Leukemia 0 0
Childhood T Acute Lymphoblastic Leukemia 0 0
Untreated Childhood Acute Lymphoblastic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Asparaginase
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Etoposide
Other interventions - Filgrastim
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Lestaurtinib
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Methylprednisolone
Treatment: Drugs - Pegaspargase
Other interventions - Pharmacological Study
Treatment: Drugs - Prednisone
Treatment: Drugs - Therapeutic Hydrocortisone
Treatment: Drugs - Vincristine Sulfate

Experimental: Arm A (standard risk MLL-G) - Population Description: Eligible patients with MLL-G (germline, or non-rearranged)

Active Comparator: Arm B (IR/HR MLL-R chemotherapy) - Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.

Experimental: Arm C (IR/HR MLL-R chemotherapy and lestaurtinib) - Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.


Treatment: Drugs: Asparaginase
Given IV, IM, or PO

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Cytarabine
Given IV or IT

Treatment: Drugs: Daunorubicin Hydrochloride
Given IV

Treatment: Drugs: Dexamethasone
Given IV or PO

Treatment: Drugs: Etoposide
Given IV

Other interventions: Filgrastim
Given IV or SC

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Lestaurtinib
Given PO

Treatment: Drugs: Leucovorin Calcium
Given IV

Treatment: Drugs: Mercaptopurine
Given PO

Treatment: Drugs: Methotrexate
Given IV, IT, or PO

Treatment: Drugs: Methylprednisolone
Given IV

Treatment: Drugs: Pegaspargase
Given IM

Other interventions: Pharmacological Study
Correlative studies

Treatment: Drugs: Prednisone
Given PO

Treatment: Drugs: Therapeutic Hydrocortisone
Given IT

Treatment: Drugs: Vincristine Sulfate
Given IV

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2) - EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto.
Timepoint [1] 0 0
From start of post-induction therapy for up to 10 years
Secondary outcome [1] 0 0
Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2 - Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. EFS will be compared between patients on treatment Arm C at DL2 to those on Arm B.
Timepoint [1] 0 0
From start of post-induction therapy for up to 10 years.
Secondary outcome [2] 0 0
Number of Patients Who Experienced Lestaurtinib-related Dose Limiting Toxicity (DLT) - Lestaurtinib-related dose-limiting toxicity proportions, as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, will by summarized by dose level for Safety phase patients.
Timepoint [2] 0 0
Up to 12 weeks from start of induction
Secondary outcome [3] 0 0
Pharmacokinetic AGP Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy - Pharmacokinetic AGP levels in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data.
Timepoint [3] 0 0
Up to 12 weeks
Secondary outcome [4] 0 0
Pharmacokinetic Albumin in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy - Pharmacokinetic albumin in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data.
Timepoint [4] 0 0
Up to 12 weeks
Secondary outcome [5] 0 0
Pharmacodynamics PIA Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy - Summarized with mean and standard deviation for those with available data in Arm C
Timepoint [5] 0 0
Sampled between weeks 6-12 from start of induction
Secondary outcome [6] 0 0
Describe FLT3 Protein Expression as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts - Described via mean and standard deviation by group.
Timepoint [6] 0 0
Sampled at the start of induction
Secondary outcome [7] 0 0
Describe FLT3 Protein Expression as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts - Described via means and standard deviations in available Arm C relapse samples
Timepoint [7] 0 0
At relapse (up to 3 years)
Secondary outcome [8] 0 0
Describe in Vitro Sensitivity as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts - Described via means and standard deviations in samples which have primary resistance to lestaurtinib
Timepoint [8] 0 0
Sampled at the start of induction
Secondary outcome [9] 0 0
Describe in Vitro Sensitivity as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts - Described via means and standard deviations in samples which have acquired resistance to lestaurtinib
Timepoint [9] 0 0
At relapse (up to 3 years)
Secondary outcome [10] 0 0
Percent Probability of Event Free Survival (EFS) by MRD Status and Treatment Arm - Three-year EFS estimates and 90% CI will be reported by treatment arm and end-induction MRD status.
Timepoint [10] 0 0
3 Years from end of Induction)
Secondary outcome [11] 0 0
Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With Survival Outcomes - EFS outcomes will be reported by genotype.
Timepoint [11] 0 0
At 3 years
Secondary outcome [12] 0 0
Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With PIA Values - Means and standard deviations of Plasma Inhibitory Activity (PIA) will be given by genotype
Timepoint [12] 0 0
At 3 years
Secondary outcome [13] 0 0
Percent Probability for Event-free Survival (EFS) for Patients on Arm A - EFS time is defined as time from treatment assignment to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto.
Timepoint [13] 0 0
From start of post-induction therapy for up to 10 years

Eligibility
Key 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 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 with mature B-cell ALL or acute myelogenous leukemia (AML) are NOT eligible

- Patients with Down syndrome are NOT eligible

- 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
Minimum age
No limit
Maximum age
1 Year
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Hawaii
Country [12] 0 0
United States of America
State/province [12] 0 0
Idaho
Country [13] 0 0
United States of America
State/province [13] 0 0
Illinois
Country [14] 0 0
United States of America
State/province [14] 0 0
Indiana
Country [15] 0 0
United States of America
State/province [15] 0 0
Iowa
Country [16] 0 0
United States of America
State/province [16] 0 0
Kentucky
Country [17] 0 0
United States of America
State/province [17] 0 0
Louisiana
Country [18] 0 0
United States of America
State/province [18] 0 0
Maine
Country [19] 0 0
United States of America
State/province [19] 0 0
Maryland
Country [20] 0 0
United States of America
State/province [20] 0 0
Massachusetts
Country [21] 0 0
United States of America
State/province [21] 0 0
Michigan
Country [22] 0 0
United States of America
State/province [22] 0 0
Minnesota
Country [23] 0 0
United States of America
State/province [23] 0 0
Mississippi
Country [24] 0 0
United States of America
State/province [24] 0 0
Missouri
Country [25] 0 0
United States of America
State/province [25] 0 0
Nebraska
Country [26] 0 0
United States of America
State/province [26] 0 0
Nevada
Country [27] 0 0
United States of America
State/province [27] 0 0
New Hampshire
Country [28] 0 0
United States of America
State/province [28] 0 0
New Jersey
Country [29] 0 0
United States of America
State/province [29] 0 0
New Mexico
Country [30] 0 0
United States of America
State/province [30] 0 0
New York
Country [31] 0 0
United States of America
State/province [31] 0 0
North Carolina
Country [32] 0 0
United States of America
State/province [32] 0 0
North Dakota
Country [33] 0 0
United States of America
State/province [33] 0 0
Ohio
Country [34] 0 0
United States of America
State/province [34] 0 0
Oklahoma
Country [35] 0 0
United States of America
State/province [35] 0 0
Oregon
Country [36] 0 0
United States of America
State/province [36] 0 0
Pennsylvania
Country [37] 0 0
United States of America
State/province [37] 0 0
Rhode Island
Country [38] 0 0
United States of America
State/province [38] 0 0
South Carolina
Country [39] 0 0
United States of America
State/province [39] 0 0
South Dakota
Country [40] 0 0
United States of America
State/province [40] 0 0
Tennessee
Country [41] 0 0
United States of America
State/province [41] 0 0
Texas
Country [42] 0 0
United States of America
State/province [42] 0 0
Utah
Country [43] 0 0
United States of America
State/province [43] 0 0
Vermont
Country [44] 0 0
United States of America
State/province [44] 0 0
Virginia
Country [45] 0 0
United States of America
State/province [45] 0 0
Washington
Country [46] 0 0
United States of America
State/province [46] 0 0
West Virginia
Country [47] 0 0
United States of America
State/province [47] 0 0
Wisconsin
Country [48] 0 0
Canada
State/province [48] 0 0
Alberta
Country [49] 0 0
Canada
State/province [49] 0 0
British Columbia
Country [50] 0 0
Canada
State/province [50] 0 0
Manitoba
Country [51] 0 0
Canada
State/province [51] 0 0
Newfoundland and Labrador
Country [52] 0 0
Canada
State/province [52] 0 0
Nova Scotia
Country [53] 0 0
Canada
State/province [53] 0 0
Ontario
Country [54] 0 0
Canada
State/province [54] 0 0
Quebec
Country [55] 0 0
Canada
State/province [55] 0 0
Saskatchewan
Country [56] 0 0
New Zealand
State/province [56] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT00557193
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joanne Hilden
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications