Phase 2 Study of Temozolomide to Treat Poor Risk / Refractory Acute Myeloid Leukemia

This is a single institution phase 2 clinical trial evaluating the efficacy, safety, and tolerability of tailored temozolomide therapy for patients with acute myeloid leukemia (AML) and poor risk features.

Patients will be assigned to 1 of 2 parallel treatment groups based on their AGAT promoter region methylation status, as determined by PCR.

Patients achieving a complete remission after 1 to 2 cycles of chemotherapy will be eligible to receive up to an additional 5 cycles of temozolomide of 5 or 19 days, depending on the methylation status of the AGAT promoter (consolidation phase).

Inclusion criteria

• Patients must have histologically or cytologically confirmed Acute Myeloid Leukemia, as defined by the WHO classification.
• Patients must be considered unfit for conventional induction chemotherapy, unwilling to receive such treatment or have evidence of disease relapse or refractory disease.
• 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).
• Age > 60 years of age.
• Life expectancy of greater than 3 months.
• ECOG performance status greater than 2.
• Patients must have normal organ and marrow function as defined below:
• Adequate hepatic function: Total bilirubin 1.5mg/dL, AST(SGOT)/ALT(SGPT) 2.5 X institutional upper limit of normal.
• 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.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

• 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.
• Patients may not be receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or DTIC
• History of gastrointestinal disease or significant bowel resection that could interfere with drug absorption.
• 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.
• Prior allogeneic stem cell transplantation.
• Inability to swallow tablets
• Prior radiation up to more than 25% of bone marrow.