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Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00720109
First received: July 19, 2008
Last updated: May 20, 2013
Last verified: May 2013
History of Changes
  Purpose

This phase 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.


Condition Intervention Phase
Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia
Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
 Drug: asparaginase
Drug: dasatinib
Drug: daunorubicin hydrochloride
Drug: prednisone
Drug: methylprednisolone
Drug: methotrexate
Drug: cytarabine
Drug: etoposide
Drug: ifosfamide
Biological: filgrastim
Drug: leucovorin calcium
Drug: cyclophosphamide
Drug: pegaspargase
Drug: dexamethasone
Drug: mercaptopurine
Radiation: radiation therapy
Drug: hydrocortisone sodium succinate
Drug: vincristine sulfate
Other: laboratory biomarker analysis
 Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intensified Tyrosine Kinase Inhibitor Therapy (Dasatinib: IND# 73969, NSC# 732517) in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:

Drug Information available for: Dexamethasone Hydrocortisone acetate Cyclophosphamide Hydrocortisone Prednisolone Mercaptopurine Prednisolone acetate Prednisone Methylprednisolone acetate Methotrexate Methylprednisolone Succinic acid Prednisolone sodium phosphate Hydrocortisone sodium succinate Cytarabine Prednisolone phosphate Hydrocortisone cypionate Dexamethasone acetate Leucovorin calcium Prednisolone sodium succinate Vincristine sulfate Methylprednisolone sodium succinate Dexamethasone sodium phosphate Ifosfamide Asparaginase Hydrocortisone butyrate Sodium succinate Sulfate ion Methotrexate sodium Daunorubicin Daunorubicin hydrochloride Etoposide Hydrocortisone valerate Levoleucovorin Hydrocortisone probutate Etoposide phosphate Filgrastim Pegaspargase Lenograstim Granulocyte colony-stimulating factor Dasatinib Daunorubicin citrate
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Feasibility of an intensified chemotherapeutic regimen incorporating dasatinib for treatment of children and adolescents with Ph+ ALL assessed by examining adverse events [ Time Frame: Up to 131 weeks of study treatment ] [ Designated as safety issue: Yes ]
    Feasibility will be defined as the ability to safely add dasatinib to the AALL0031 chemotherapy backbone either when given discontinuously (in 2-week periods followed by 1 to 2 weeks off) or continuously.

  • Toxicity of an intensified chemotherapeutic regimen incorporating dasatinib for treatment of children and adolescents with Ph+ ALL as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: From the time of first treatment, assessed up to 7 years ] [ Designated as safety issue: Yes ]
  • EFS of patients with standard-risk disease treated with dasatinib in combination with intensified chemotherapy [ Time Frame: At 3 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Contribution of dasatinib on minimal residual disease (MDR) after induction therapy [ Time Frame: At 5 weeks ] [ Designated as safety issue: No ]
    A sample of 120 on this study will give 80.5% power to detect a reduction of 18% (71% versus 53%) in the MRD positivity rate, due to the addition of 2 weeks of dasatinib during Induction (2 sample Z-test of proportions, 1-sided test, alpha=5%).

  • Impact on MRD levels at the end of consolidation block 2 [ Time Frame: At 11 weeks ] [ Designated as safety issue: No ]
    A 1-sample Z-test of proportions (alpha=5%, 1-sided test) will be used.

  • Overall EFS rate for the combined cohort of Standard- and High-Risk patients (who receive the final chosen dose of dasatinib) [ Time Frame: From the time entry on study to first event or date of last follow-up, assessed up to 7 years ] [ Designated as safety issue: No ]
    An event is defined as: Induction failure, relapse at any site, secondary malignancy, or death.


Estimated Enrollment: 195
Study Start Date: July 2008
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
 Drug: asparaginase
Given IT
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: prednisone
Given PO or IV
Other Names:
  • DeCortin
  • Deltra
Drug: methylprednisolone
Given IV
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: methotrexate
Given IT, PO, or IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen
Drug: leucovorin calcium
Given IV or PO
Other Names:
  • CF
  • CFR
  • LV
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Radiation: radiation therapy
Some patients undergo cranial RT
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: hydrocortisone sodium succinate
Given IT
Other Names:
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00720109

  Show 122 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: William Slayton Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00720109     History of Changes
Other Study ID Numbers: NCI-2009-00312, AALL0622, CDR0000600217, COG-AALL0622, U10CA098543
Study First Received: July 19, 2008
Last Updated: May 20, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
6-Mercaptopurine
Cytarabine
 Methotrexate
Cyclophosphamide
Isophosphamide mustard
Pegaspargase
Asparaginase
Daunorubicin
Dexamethasone
Etoposide
Ifosfamide
Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Vincristine
BB 1101
Dasatinib

ClinicalTrials.gov processed this record on June 18, 2013