A Study of Tretinoin and Arsenic Trioxide in Treating Patients with Untreated Acute Promyelocytic Leukemia

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: 15-005293
    NCT ID: NCT02339740
    Sponsor Protocol Number: AAML1331

About this study

The purpose of this study is to assess the effectiveness and long term side effects of using combined 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.

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 newly diagnosed with a clinical diagnosis of Acute Promyelocytic Leukemia (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-RAR alpha transcript by RQ-PCR to be eligible
  • 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 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 including 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
  • 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)
  • Patients with a baseline QTc of > 450 msec (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
  • Patients with right bundle branch block plus left anterior hemiblock, bifascicular block
  • Patients with serum creatinine > 3.0 mg/dL and patients on active dialysis for renal dysfunction
  • Patients who have received treatment with any other cytotoxic chemotherapy prior to beginning protocol therapy (other than allowed in above criteria)
  • Female patients who are pregnant 
    • 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
  • 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

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Carola A Arndt, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

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CLS-20199623

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