Trial Search Results

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

This randomized phase III trial studies how well combination chemotherapy works in treating young patients with newly diagnosed B acute lymphoblastic leukemia that is likely to come back or spread, and in patients with Philadelphia chromosome (Ph)-like tyrosine kinase inhibitor (TKI) sensitive mutations. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Drug: Clofarabine
  • Drug: Cyclophosphamide
  • Drug: Cytarabine
  • Drug: Dasatinib
  • Drug: Dexamethasone
  • Drug: Doxorubicin Hydrochloride
  • Drug: Etoposide
  • Drug: Hydrocortisone Sodium Succinate
  • Other: Laboratory Biomarker Analysis
  • Drug: Leucovorin Calcium
  • Drug: Mercaptopurine
  • Drug: Methotrexate
  • Drug: Pegaspargase
  • Drug: Prednisone
  • Radiation: Radiation Therapy
  • Drug: Thioguanine
  • Drug: Vincristine Sulfate

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   - Patients must be enrolled on AALL08B1 or APEC14B1 (if available for ALL patients)
   prior to enrollment on AALL1131

   - White Blood Cell Count (WBC) Criteria

      - Age 1-9.99 years: WBC >= 50 000/uL

      - Age 10-30.99 years: Any WBC

      - Age 1-30.99 years: Any WBC with:

         - Testicular leukemia

         - CNS leukemia (CNS3)

         - Steroid pretreatment

   - Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health
   Organization [WHO] classification) (also termed B-precursor acute lymphoblastic
   leukemia); patients with Down syndrome are also eligible

   - Organ function requirements for patients with Ph-like ALL and a predicted
   TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase
   mutation must have assessment of organ function performed within 3 days of study entry
   onto the dasatinib arm of AALL1131

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

      - Age: Maximum Serum Creatinine (mg/dL)

      - 1 to < 6 months: 0.4 (male) 0.4 (female)

      - 6 months to < 1 year: 0.5 (male) 0.5 (female)

      - 1 to < 2 years: 0.6 (male) 0.6 (female)

      - 2 < 6 years: 0.8 (male) 0.8 (female)

      - 6 to < 10 years: 1.0 (male) 1.0 (female)

      - 10 to < 13 years: 1.2 (male) 1.2 (female)

      - 13 to < 16 years: 1.5 (male) 1.4 (female)

      - > 16 years: 1.7 (male) 1.4 (female)

   - Direct bilirubin =< 3 x upper limit of normal (ULN) for age, and

   - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 10 x
   upper limit of normal (ULN) for age

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

      - Patients must have an electrocardiogram (EKG) fewer than 6 days prior to
      enrollment on the dasatinib arm; patients who have had cardiac assessments by
      echocardiogram or radionuclide scan at the beginning of induction do not need to
      have these repeated prior to study entry; correct QT interval (QTc) < 450 msec on
      baseline electrocardiogram as measured by the Frederica or Bazett formula

      - No major conduction abnormality (unless a cardiac pacemaker is present)

   - 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

   - Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive
   Functioning study

      - Patients must be aged 6 to 13 years at time of B-ALL diagnosis, enrolled on
      AALL1131

      - Patients must be English-, French- or Spanish-speaking (languages in which the
      assessment is available)

      - Patients must have no known history of neurodevelopmental disorder prior to
      diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William's Syndrome, mental
      retardation)

      - Patients must have no significant visual impairment that would prevent computer
      use and recognition of the visual test stimuli

   - Eligibility criteria for the National Cancer Institute (NCI) standard risk patients
   from AALL0932 enrolling on this study at the end of Induction

   - Patients enrolled on AALL0932, without Down syndrome, meeting the following criteria
   will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the HR
   B-ALL stratum of this study at the end of Induction:

      - Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day
      8 peripheral blood (PB) minimal residual disease (MRD) >= 1% and day 29 BM MRD <
      0.01%

      - With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any day 8
      PB MRD and day 29 bone marrow (BM) MRD >= 0.01%

      - Both NCI standard risk (SR) and HR patients without Down syndrome and with
      testicular disease at diagnosis, who do not meet other VHR criteria, will be
      eligible for the HR stratum

   - Effective Amendment 6, patients enrolled on AALL0932, without Down syndrome, meeting
   the following criteria will NOT be eligible to continue on AALL0932 or the VHR stratum
   of AALL1131:

      - Intrachromosomal amplification of chromosome 21 (iAMP21)

      - Mixed-lineage leukemia (MLL) rearrangement

      - Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index <
      0.81)

      - Induction failure (M3 BM at day 29)

      - Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day
      29 BM MRD >= 0.01%

   - Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria will
   NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS HR
   B-ALL stratum of this study at the end of Induction:

      - Day 29 MRD >= 0.01%

      - MLL rearrangement

      - Hypodiploidy (n < 45 chromosomes and/or DNA index < 0.81)

   - DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction
   failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for
   post-Induction therapy on either trial (AALL0932 or AALL1131)

   - All patients and/or their parents or legal guardians must sign a written informed
   consent

   - All institutional, Food and Drug Administration (FDA), and NCI requirements for human
   studies must be met

Exclusion Criteria:

   - With the exception of steroid pretreatment or the administration of intrathecal
   cytarabine, patients must not have received any prior cytotoxic chemotherapy for
   either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation
   of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed
   after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving
   prior steroid therapy may be eligible for AALL1131

   - Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this
   study but may be eligible to enroll in a successor Children's Oncology Group (COG)
   Philadelphia positive (Ph+) ALL trial by day 15 Induction

   - DS HR B-ALL patients with Induction failure or BCR-ABL1

   - Female patients who are pregnant are ineligible

   - Lactating females are not eligible unless they have agreed not to breastfeed their
   infant

   - Female patients of childbearing potential are not eligible unless a negative pregnancy
   test result has been obtained

   - Sexually active patients of reproductive potential are not eligible unless they have
   agreed to use an effective contraceptive method for the duration of their study
   participation

Ages Eligible for Study

1 Year - 30 Years

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Christina Baggott
650-497-7659
Recruiting