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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00720109




Registration number
NCT00720109
Ethics application status
Date submitted
19/07/2008
Date registered
22/07/2008
Date last updated
13/04/2020

Titles & IDs
Public title
Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Scientific title
Intensified Tyrosine Kinase Inhibitor Therapy (Dasatinib NSC# 732517) in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL)
Secondary ID [1] 0 0
NCI-2009-00312
Secondary ID [2] 0 0
NCI-2009-00312
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia 0 0
Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 0 0
Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 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 - Dasatinib
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Etoposide
Other interventions - Filgrastim
Treatment: Drugs - Hydrocortisone Sodium Succinate
Treatment: Drugs - Ifosfamide
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Methylprednisolone
Treatment: Drugs - Pegaspargase
Treatment: Drugs - Prednisone
Treatment: Other - Radiation Therapy
Treatment: Drugs - Vincristine Sulfate

Experimental: Treatment (enzyme inhibitor therapy and chemotherapy) - See Detailed Description


Treatment: Drugs: Asparaginase
Given IT

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Cytarabine
Given IT or IV

Treatment: Drugs: Dasatinib
Given PO

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

Treatment: Drugs: Hydrocortisone Sodium Succinate
Given IT

Treatment: Drugs: Ifosfamide
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Leucovorin Calcium
Given IV or PO

Treatment: Drugs: Mercaptopurine
Given PO

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

Treatment: Drugs: Methylprednisolone
Given IV

Treatment: Drugs: Pegaspargase
Given IM

Treatment: Drugs: Prednisone
Given PO or IV

Treatment: Other: Radiation Therapy
Some patients undergo cranial RT

Treatment: Drugs: Vincristine Sulfate
Given IV

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival (EFS) of Patients With Standard-risk Disease Treated With Dasatinib in Combination With Intensified Chemotherapy - Event-Free Survival (EFS) curves will be constructed using the Kaplan-Meier life table method with standard errors computed using the method of Peto and Peto. A 1-sided 95% confidence interval for EFS will be constructed.
Timepoint [1] 0 0
At 3 years
Primary outcome [2] 0 0
Feasibility and Toxicity of an Intensified Chemotherapeutic Regimen Incorporating Dasatinib for Treatment of Children and Adolescents With Ph+ ALL Assessed by Examining Adverse Events - Number of patients in safety cohort with dose limiting toxicity (DLT)(including treatment delay)
Timepoint [2] 0 0
Weeks 3 through 23 of treatment (From week 3 Induction through Intensification Block 1)
Secondary outcome [1] 0 0
Contribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy - Percent of patients MRD Positive (MRD > 0.01%) at End of Induction.
Timepoint [1] 0 0
At the end of induction therapy (at 5 weeks)
Secondary outcome [2] 0 0
Percent of Patients MRD Positive (MRD > 0.01%) at End of Consolidation - A 1-sample Z-test of proportions (alpha=5%, 1-sided test) will be used.
Timepoint [2] 0 0
At end of consolidation (at 11 weeks)
Secondary outcome [3] 0 0
Overall EFS Rate for the Combined Cohort of Standard- and High-Risk Patients (Who Receive the Final Chosen Dose of Dasatinib) - An event is defined as: Induction failure, relapse at any site, secondary malignancy, or death.
Timepoint [3] 0 0
From the time entry on study to first event or date of last follow-up, assessed up to 7 years

Eligibility
Key inclusion criteria
- Newly diagnosed acute lymphoblastic leukemia (ALL)

- Definitive evidence of BCR-ABL fusion (Philadelphia chromosome positive [PH+])
from an approved Children's Oncology Group (COG) cytogenetics laboratory

- Meets one of the following criteria:

- Concurrent enrollment on Clusters of Orthologous Groups (COG)-AALL03B1 (or a
successor trial) AND COG-AALL0232, COG-AALL0331, COG-AALL0434 or other front-line
COG ALL clinical trial

- Concurrent enrollment on COG-AALL03B1 (or a successor trial) AND scheduled to
receive a 3 or 4-drug standard induction regimen

- Concurrent enrollment on a Dana-Farber Cancer Institute (DFCI) Childhood ALL
Consortium trial (or scheduled to be treated as per a DFCI Childhood ALL
Consortium induction regimen)

- All patients must have definitive evidence of BCR-ABL fusion from an approved COG
cytogenetics laboratory; patients may NOT have received Day 15 of Induction
chemotherapy (or day 18 vincristine if enrolled on a DFCI Childhood ALL Consortium
trial) prior to enrollment on AALL0622

- Patients must have a performance status of 0, 1 or 2 at completion of two weeks of
Induction; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16
years of age

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73
m^2 or maximum serum creatinine based on age and gender as follows:

- 0.4 mg/dL (for patients 1 to 5 months of age)

- 0.5 mg/dL (for patients 6 to 11 months of age)

- 0.6 mg/dL (for patients 1 year of age)

- 0.8 mg/dL (for patients 2 to 5 years of age)

- 1.0 mg/dL (for patients 6 to 9 years of age)

- 1.2 mg/dL (for patients 10 to 12 years of age)

- 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)

- 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)

- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5
times ULN for age

- Shortening fraction >= 27% by echocardiogram or ejection fraction >= 50% by gated
radionuclide study

- No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% at
sea level if there is clinical indication for determination

- Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine,
phenytoin, primidone, phenobarbital) should be avoided

- Patients will start AALL0622 therapy on day 15 of induction therapy (or day 18 if
enrolled on a DFCI Childhood ALL Consortium trial); patients must have received the
first 2 weeks of Induction therapy
Minimum age
2 Years
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Females of childbearing potential must have a negative pregnancy test; patients of
childbearing potential must agree to use an effective birth control method

- Female patients who are lactating must agree to stop breast-feeding

- Patients with Down syndrome

- Patients with any clinically significant cardiovascular disease including the
following:

- Myocardial infarction or ventricular tachyarrhythmia within 6 months

- Ejection fraction less than institutional normal

- Major conduction abnormality (unless a cardiac pacemaker is present)

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Single group
Other design features
Phase
Phase 2/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)
QLD,SA,WA
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [2] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [3] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [4] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
5006 - North Adelaide
Recruitment postcode(s) [3] 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
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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
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Hawaii
Country [12] 0 0
United States of America
State/province [12] 0 0
Idaho
Country [13] 0 0
United States of America
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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
Kentucky
Country [16] 0 0
United States of America
State/province [16] 0 0
Louisiana
Country [17] 0 0
United States of America
State/province [17] 0 0
Maryland
Country [18] 0 0
United States of America
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Massachusetts
Country [19] 0 0
United States of America
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Michigan
Country [20] 0 0
United States of America
State/province [20] 0 0
Minnesota
Country [21] 0 0
United States of America
State/province [21] 0 0
Mississippi
Country [22] 0 0
United States of America
State/province [22] 0 0
Missouri
Country [23] 0 0
United States of America
State/province [23] 0 0
Nebraska
Country [24] 0 0
United States of America
State/province [24] 0 0
Nevada
Country [25] 0 0
United States of America
State/province [25] 0 0
New Jersey
Country [26] 0 0
United States of America
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New Mexico
Country [27] 0 0
United States of America
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New York
Country [28] 0 0
United States of America
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North Carolina
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United States of America
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North Dakota
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United States of America
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Ohio
Country [31] 0 0
United States of America
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Oklahoma
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United States of America
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Oregon
Country [33] 0 0
United States of America
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Pennsylvania
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United States of America
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Rhode Island
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United States of America
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Tennessee
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United States of America
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Texas
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Utah
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Virginia
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Washington
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West Virginia
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United States of America
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Wisconsin
Country [42] 0 0
Canada
State/province [42] 0 0
British Columbia
Country [43] 0 0
Canada
State/province [43] 0 0
Manitoba
Country [44] 0 0
Canada
State/province [44] 0 0
Nova Scotia
Country [45] 0 0
Canada
State/province [45] 0 0
Ontario
Country [46] 0 0
Canada
State/province [46] 0 0
Quebec
Country [47] 0 0
Canada
State/province [47] 0 0
Saskatchewan
Country [48] 0 0
New Zealand
State/province [48] 0 0
Auckland
Country [49] 0 0
New Zealand
State/province [49] 0 0
Christchurch
Country [50] 0 0
Puerto Rico
State/province [50] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This phase II/III trial is studying the side effects and how well giving dasatinib together
with combination chemotherapy works in treating young patients with newly diagnosed acute
lymphoblastic leukemia (ALL). Dasatinib may stop the growth of cancer cells by blocking some
of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to
stop the growth of cancer cells, either by killing the cells or by stopping them from
dividing. Giving dasatinib together with combination chemotherapy may kill more cancer cells.
Trial website
https://clinicaltrials.gov/show/NCT00720109
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
William B Slayton
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