Phase 2 Study of Temozolomide to Treat Poor Risk / Refractory Acute Myeloid Leukemia
Condition: Leukemia, Myeloid
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Temozolomide
Intervention description: Priming, Group 2 only, 100 mg/m2/day temozolomide.
Induction (both arms) 200 mg/m2/day temozolomide
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No

Summary:

      Open-label, non-randomized, parallel assignment, phase 2 trial assessing the safety and
      efficacy of distinct temozolomide treatment regimens for patients with AML and poor prognosis
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have histologically or cytologically confirmed Acute Myeloid Leukemia,
             as defined by the WHO classification.

          2. Patients must be considered unfit for conventional induction chemotherapy, unwilling
             to receive such treatment or have evidence of disease relapse or refractory disease.

          3. For patients who have received no prior conventional chemotherapy, one of the
             following must be present:

               -  Poor risk cytogenetics (complex abnormalities, deletions of chromosome 7 or 5,
                  11q23 abnormalities, inv[3])

               -  Secondary leukemia (prior hematologic disorder or therapy-related leukemia).

          4. Age > 60 years of age.

          5. Life expectancy of greater than 3 months.

          6. ECOG performance status greater than 2.

          7. Patients must have normal organ and marrow function as defined below:

          8. Adequate hepatic function: Total bilirubin 1.5mg/dL, AST(SGOT)/ALT(SGPT) 2.5 X
             institutional upper limit of normal.

          9. Adequate renal function: serum creatinine within normal institutional limits or
             Calculated creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine
             levels above institutional normal.

         10. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier.

          2. Patients may not be receiving any other investigational agents.

          3. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to temozolomide or DTIC

          4. History of gastrointestinal disease or significant bowel resection that could
             interfere with drug absorption.

          5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          6. Prior allogeneic stem cell transplantation.

          7. Inability to swallow tablets

          8. Prior radiation up to more than 25% of bone marrow.