Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy
Condition: Acute Promyelocytic Leukemia
MeSH terms: Leukemia; Leukemia, Promyelocytic, Acute
Intervention: Tretinoin and Arsenic Trioxide
Intervention description: See Detailed Description
Intervention MeSH terms: Arsenic Trioxide; Tretinoin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Tretinoin; all-trans retinoic acid; ATRA; Vesanoid; Arsenic Trioxide; ATO; Trisenox; 11-040

Summary:

      The purpose of this study is to find what effects, good and/or bad, treatment with two drugs
      has on leukemia. The first medicine is tretinoin (also called all-trans retinoic acid, ATRA,
      or Vesanoid). It is an approved medicine that causes the leukemia cells in APL to mature. It
      is related to vitamin A. The second is arsenic trioxide (Trisenox). It is an approved
      medicine for APL that comes back after earlier treatment.

      APL is most often treated with tretinoin and standard chemotherapy drugs. These chemotherapy
      drugs can cause infection and bleeding. They can also damage the heart and normal bone marrow
      cells. This can lead to a second leukemia years later.

      In this study, the investigators are using tretinoin and arsenic trioxide together. Both
      drugs work to treat APL. They have been used together in only a limited number of people. The
      investigators want to use these drugs together to reduce the amount of standard chemotherapy
      and decrease side effects. The patient will receive standard chemotherapy with a drug called
      idarubicin only if they have a higher chance of the leukemia coming back or a higher risk of
      side effects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously untreated patients with a morphologic diagnosis of APL, confirmed by
             demonstration of t(15;17) using conventional cytogenetics OR florescence in situ
             hybridization (FISH), OR a positive RT-PCR assay for PML-RAR at the subject's local
             institution.

          -  Age ≥18 years. Karnofsky performance status of ≥ 60%.

          -  Adequate renal function as demonstrated by a serum creatinine ≤ 2.0 mg/dl or a
             creatinine clearance of > 60 ml/min.

          -  Adequate hepatic function as demonstrated by a bilirubin < 2.0 mg/dl (unless
             attributable to Gilbert's disease) and an alkaline phosphatase, AST, and ALT ≤ 2.5
             times the upper limit of normal.

          -  Normal cardiac function as demonstrated by a left ventricular ejection fraction ≥ 50%
             on echocardiogram or MUGA scan.

          -  QTc ≤ 500 msec on baseline ECG.

          -  Negative serum pregnancy test in women of childbearing potential.

          -  Ability to swallow oral medication.

          -  Men and women of child-bearing potential must be willing to practice an effective
             method of birth control during treatment and at least 4 months after treatment is
             finished.

          -  Patients with central nervous system involvement by APL are eligible and may receive
             concomitant treatment with radiation therapy and/or intrathecal chemotherapy in
             accordance with standard medical practice.

        Exclusion Criteria:

          -  Previous treatment for APL, except tretinoin, which may be given for up to 7 days
             prior to study entry.

          -  Active serious infections not controlled by antibiotics.

          -  Pregnant women or women who are breast-feeding.

          -  Concurrent active malignancy requiring immediate therapy.

          -  Clinically significant cardiac disease (NY Heart Association Class III or IV),
             including chronic arrhythmias, or pulmonary disease.

          -  Other serious or life-threatening conditions deemed unacceptable by the principal
             investigator.