Trial of Arsenic Trioxide With Ascorbic Acid in the Treatment of Adult Non-Acute Promyelocytic Leukemia (APL) Acute Myelogenous Leukemia
Condition: Acute Myelogenous Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Arsenic Trioxide (ATO); Ascorbic Acid
Intervention description: Arsenic Trioxide .25 mg/kg/day; Ascorbic Acid 1000 mg every other day for 25 days
Intervention MeSH terms: Ascorbic Acid; Arsenic Trioxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This clinical research study is for patients with acute myelogenous leukemia (in short AML)
      that did not respond to previous treatment or unable to receive chemotherapy.

      Arsenic has been used as a drug for many centuries. While arsenic containing drugs were used
      in the past for cancer treatments, the major use of arsenic in western countries has been for
      the treatment of uncommon tropical illnesses, such as sleeping sickness. Recently, some new
      information suggests that arsenic in a form called arsenic trioxide may also be useful to
      treat some cancers of the blood, such as leukemia, lymphoma and myeloma. Studies from China
      and the USA showed that patients with a type of blood cancer called acute promyelocytic
      leukemia, whose disease failed to respond to other treatments, responded very well to arsenic
      trioxide. Studies done in laboratories in the United States have shown that arsenic can kill
      AML cells growing in culture dishes.

      Ascorbic acid (vitamin C), a natural supplement in our diet, has long been involved with
      cancer prevention. Laboratory tests have shown that although arsenic trioxide by itself can
      kill AML cells in the test tube, when vitamin C is added to arsenic trioxide in a test tube,
      the death of the leukemia cells increases significantly.

      The purpose of this study is to find out if the combination of arsenic trioxide (Trisenox)
      and ascorbic acid is effective in the treatment of patients who have AML. The second purpose
      is to study how the two drugs affect cells in the laboratory. Samples from the blood and bone
      marrow (the part of the body that makes blood cells) will be collected, at specific times
      during treatment, in order to study them in the laboratory. By studying blood and marrow
      cells, researchers hope to learn the mechanisms by which the drugs work.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of non-APL AML (FAB subtypes M0 - M7 but excluding M3) confirmed by
             myeloperoxidase stain and/or flow cytometry.

          -  For patients of age 18 or older - only refractory or relapsed AML will be included.
             Refractory disease is defined as newly diagnosed patients who fulfill ONE of the
             following criteria:

               -  Patient aged 60 years or younger, who have failed to achieve a complete remission
                  after at least two cycles of front line induction chemotherapy.

               -  Patients of any age who have AML, that is post myelodysplastic syndrome (MDS),
                  who failed to achieve a complete remission after at least one cycle of front line
                  induction chemotherapy.

               -  Patients aged 60 years or older who failed to achieve a complete remission after
                  at least one cycle of front line induction chemotherapy.

          -  Newly diagnosed patients aged 55 or older who will not receive intensive anti-leukemia
             chemotherapy can also be enrolled.

          -  Post-myelodysplasia AML and secondary AML are included.

          -  Stem cell transplantation failures are included.

          -  Karnofsky performance status greater or equal to 50%.

          -  Adequate renal function (creatinine < 1.5 x ULN or creatinine clearance > 60 ml/min)
             and hepatic function (transaminases < 2.5 x ULN, serum total bilirubin < 3 mg/dl).

          -  Females of childbearing potential must have a negative serum pregnancy test prior to
             enrollment on the study, and both women and men must use an effective birth control
             method while on the study.

          -  Signed consent.

        Exclusion Criteria:

          -  Newly diagnosed patients older than age 55 who:

               -  Refuse chemotherapy when their treating physician recommends standard
                  anti-leukemia induction chemotherapy.

               -  Have a Karnofsky performance status of greater or equal to 70%, aged < 75 years
                  and has no prior myelodysplastic syndrome.

               -  Have a risk/benefit ratio that gives their treating physician good reason for
                  administration of standard anti-leukemia induction chemotherapy.

          -  Patients who have already been treated with arsenics.

          -  CML in blastic crisis.

          -  Patients with cardiopathies including recurrent supraventricular arrhythmia and any
             type of sustained ventricular arrhythmia or conduction block (A-V block grade II or
             III, LBBB).

          -  Patients with HIV.

          -  Pregnant or breastfeeding women.

          -  QT interval > 460 msec in the presence of serum potassium > 4.0 mEq/L and magnesium >
             1.8 mg/dL.

          -  Pre-existing neurotoxicity/neuropathy of Grade 2 or greater according to the NCI
             Common Toxicity Criteria Version 2.

          -  History of preexisting neurological disorders (grade 3 or higher by the NCI Common
             Toxicity Criteria; in particular, seizure disorders).

          -  Patients with an underlying medical condition that could be aggravated by the
             treatment or life threatening disease unrelated to AML as evaluated by the enrolling
             physician.

          -  Patients with active second malignancy, excluding adequately treated basal or squamous
             cell carcinoma of the skin, or carcinoma in situ of the cervix.

          -  Inability or unwillingness to comply with the treatment protocol.