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

Overview

  • Study type

    Interventional
  • Study phase

    III
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 11-007833
    NCT ID: NCT01406756, NCT02883049
    Sponsor Protocol Number: AALL1131

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Patients must be enrolled on AALL08B1 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 dasatinib-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry to be eligible for 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 Incidence and Natural History of Osteonecrosis study
    • Patients must be 10 years of age or greater at the time of B-ALL diagnosis, enrolled on AALL1131
    • Patients with Down syndrome or Ph-like with a predicted TKI-sensitive mutation are not eligible
  • Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive Functioning study
    • Patients must be aged 6 to 11 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
  • 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 VHR B-ALL stratum of this study at the end of Induction:
    • 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 ALL0932, 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

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Vilmarie Rodriguez, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

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CLS-20152035

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