Temozolomide Plus Vorinostat in Relapse/Refractory Acute Myeloid Leukemia (AML)
Condition: Acute Myeloid Leukemia With 11q23-abnormality in Relapse
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence
Intervention: Temozolomide; Vorinostat
Intervention description: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.; A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
Intervention MeSH terms: Temozolomide; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to first determine if temozolomide plus vorinostat in combination
      can control relapsed or refractory acute myeloid leukemia (AML) and determine if this
      combination can be safely taken. The study will look at the side effects of the Temozolomide
      plus Vorinostat in combination and whether the treatment schedule is tolerated.
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  Histologically- or cytologically-confirmed acute myeloid leukemia (AML)

          -  Relapsed or refractory (AML), after at least 1 prior induction regimen

          -  Age ≥ 18 years

          -  Life expectancy > 2 months.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2

          -  Calculated creatinine clearance ≤ 2.0 mg/dL (OR ≥ 30 mL/min for patients with serum
             creatinine levels > 2.0 mg/dL)

          -  Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) ≤ 2.5 X ULN

          -  Alanine aminotransferase (ALT) ≤ 2.5 X ULN

          -  Alkaline phosphatase (liver fraction) ≤ 2.5 X ULN

          -  If male, must agree to use an adequate method of contraception for the duration of the
             study and 1 month following coming off study or of study completion

          -  If female of childbearing potential, must a negative serum pregnancy test within 72
             hours prior to receiving the first dose of vorinostat.

          -  If female, must be one of the following:

               -  Post-menopausal (free from menses for ≥ 2 years),

               -  Surgically-sterilized

               -  Willing to use 2 adequate barrier methods of contraception

               -  Agree to abstain from heterosexual activity throughout the study, starting with
                  Visit 1

          -  Available at the treating institution for study assessments and procedures for the
             duration of the study

          -  Written informed consent

        EXCLUSION CRITERIA

          -  Received chemotherapy; radiotherapy; or biological therapy within 30 days (42 days for
             nitrosoureas or mitomycin C) prior to initial dosing with study drug(s), or has not
             recovered from adverse events due to agents administered more than 30 days earlier,
             except for hydroxyurea-related adverse events.

          -  Currently participating or within 30 days of initial dosing with study drug(s), has
             participated in a study with an investigational compound or device

          -  Receiving any other investigational agents or concomitant radiotherapy, chemotherapy,
             or immunotherapy.

          -  Received a histone deacetylase (HDAC) inhibitor [eg, romidepsin (Depsipeptide),
             NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103, CRA024781, etc]
             within the past 30 days. Patients who have received valproic acid or other compounds
             with HDAC inhibitor-like activity, as anti-tumor therapy should not enroll in this
             study. Patients who have received such compounds for other indications, eg, valproic
             acid for epilepsy, may enroll after a 30-day washout period.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to temozolomide; vorinostat; dacarbazine (DTIC-Dome, DIC, imidazole
             carboxamide)

          -  History of gastrointestinal disease or significant bowel resection that could
             interfere with drug absorption or inability to swallow tablets.

          -  Uncontrolled intercurrent illness (as defined by the investigators) including, but not
             limited to, ongoing or active infection (HIV, Hepatitis B or Hepatitis C), 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 within 2 months of trial enrollment or
             prior radiation up to more than 25% of bone marrow.

          -  Currently active 2nd malignancy, other than nonmelanoma skin cancer and carcinoma in
             situ of the cervix (completed therapy for a prior malignancy, and disease-free from
             prior malignancies for >5 years or are considered by their physician to be at less
             than 30% risk of relapse is not considered to be an "currently active" malignancy)

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial

          -  Pregnant or breast feeding

          -  Expecting to conceive or father children within the projected duration of the study.

          -  Uncontrolled intercurrent illness or circumstances that could limit compliance with
             the study, including, but not limited to the following: active infection, acute or
             chronic graft versus host disease, symptomatic congestive heart failure, unstable
             angina pectoris, cardiac arrhythmia, or psychiatric conditions.

          -  History or current evidence of any condition, therapy, or lab abnormality that might
             confound the results of the study, interfere with the patient's participation for the
             full duration of the study, or is not in the best interest of the patient to
             participate.