Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

Status: Recruiting
DFCI Protocol ID: 15-719

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. Pediatric Acute Myelogenous Leukemia

Conducting Institutions:

Children's Hospital Boston, Dana-Farber Cancer Institute, Massachusetts General Hospital

Overall PI:

Barbara Degar, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Howard Weinstein, MD, Massachusetts General Hospital


Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP,
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

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

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

  -  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

  -  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

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