Patients with Newly Diagnosed Acute Promyelocytic Leukemia (APL)

A Phase III Study for Patients with Newly Diagnosed Acute Promyelocytic Leukemia (APL) using Arsenic Trioxide and All-Trans Retinoic Acid

November 22, 2017

  • Clinical Trial Information

    Trial Contact: El-Shami, Jessica; Francois, Laetitia Claire; Leffin, Melissa; Spinelli, Jennifer

  • IRB No: AAML1331

    Protocol Abbrev: AAML1331

    Principal Investigator: Vincent F. Giusti, MD

    Phase: Drug: Phase III

    Age Group: Pediatric

    Secondary Protocol No: AAML1331

    Treatment: Arsenic Trioxide and All-Trans Retinoic Acid

    Therapies Involved: Medication

    ClinicalTrials.gov ID: NCT02339740

  • Objective

    This phase III trial studies tretinoin and arsenic trioxide in treating patients with newly diagnosed acute promyelocytic leukemia. Standard treatment for acute promyelocytic leukemia involves high doses of a common class of chemotherapy drugs called anthracyclines, which are known to cause long-term side effects, especially to the heart. Tretinoin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Arsenic trioxide may stop the growth of cancer cells by either killing the cells, by stopping them from dividing, or by stopping them from spreading. Completely removing or reducing the amount of anthracycline chemotherapy and giving tretinoin together with arsenic trioxide may be an effective treatment for acute promyelocytic leukemia and may reduce some of the long-term side effects.

  • Key Eligibility

    Inclusion Criteria:

    •  Patients must be newly diagnosed with a clinical diagnosis of APL (initially by morphology of bone marrow or peripheral blood)
    ◦Bone marrow is highly preferred but in cases where marrow cannot be obtained at diagnosis, peripheral blood will be accepted

    •  If the RQ-PCR results are known at the time of study enrollment, the patient must demonstrate the PML-RARalpha transcript by RQ-PCR to be eligible
    •  NOTE: A lumbar puncture is not required in order to be enrolled on study nor are lumbar punctures recommended at the time of diagnosis; if the diagnosis of APL is known or suspected, diagnostic lumbar punctures in patients with neurologic symptoms should be deferred until any coagulopathy is corrected; if central nervous system (CNS) disease is suspected or proven, a computed tomography (CT) or magnetic resonance imaging (MRI) should be considered to rule out the possibility of an associated chloroma; if CNS disease is documented, patients are still eligible and will receive protocol directed intrathecal treatments
    •  Patients may receive up to a maximum of 5 days of pre-treatment with ATRA prior to administration of protocol therapy
    •  Treatment with hydroxyurea, corticosteroids (any route) and intrathecal cytarabine prior to beginning protocol directed therapy is allowed; however, it should be noted that lumbar puncture and intrathecal therapy at initial diagnosis of APL is not recommended
    •  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

    Exclusion Criteria:
    •  Patients with secondary APL are excluded; this includes all patients with APL that may have resulted from prior treatment (chemotherapy or radiation)
    •  Patients with isolated myeloid sarcoma (myeloblastoma, chloroma, including leukemia cutis) but without evidence of APL by bone marrow or peripheral blood morphology are excluded
    •  Patients with a pre-existing diagnosis of a prolonged QT syndrome (even if corrected QT interval [QTc] is normal at the time of APL diagnosis) are excluded
    •  Patients with a baseline QTc of > 450 msec are excluded; Bazett's formula is to be used for measurement of the corrected QT interval: the QT interval (msec) divided by the square root of the RR interval (msec)
    •  Patients with a history or presence of significant ventricular or atrial tachyarrhythmia are excluded
    •  Patients with right bundle branch block plus left anterior hemiblock, bifascicular block are excluded
    •  Patients with serum creatinine > 3.0 mg/dL and patients on active dialysis for renal dysfunction are excluded
    •  Patients who have received treatment with any other cytotoxic chemotherapy prior to beginning protocol therapy (other than allowed in above criteria) are excluded
    •  Female patients who are pregnant are exclude; patients should not be pregnant or plan to become pregnant while on treatment; a pregnancy test prior to enrollment is required for female patients of childbearing potential
    •  Lactating females who plan to breastfeed their infants are excluded
    •  Sexually active patients of reproductive potential who have not agreed to be abstinent or use 2 forms of effective contraception during treatment through 1 month off therapy are excluded