Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia
Condition: Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2); PML-RARA
MeSH terms: Leukemia; Leukemia, Promyelocytic, Acute
Intervention: Arsenic Trioxide; Cytarabine; Dexamethasone; Idarubicin; Laboratory Biomarker Analysis; Mitoxantrone Hydrochloride; Quality-of-Life Assessment; Questionnaire Administration; Tretinoin
Intervention description: Given IV; Given IV; Given PO or IV; Given IV; Correlative studies; Given IV; Ancillary studies; Ancillary studies; Given PO
Intervention MeSH terms: Vitamins; Vitamin A; Cytarabine; Dexamethasone; Dexamethasone acetate; Mitoxantrone; Idarubicin; Tretinoin; Retinol palmitate; Arsenic Trioxide; BB 1101
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 158.0
Sex: All
Minimum age: 12 Months
Maximum age: 21 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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 excluded; 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