Phase II Study of Decitabine and Cytarabine for Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: decitabine and cytarabine; Supportive Care
Intervention description: blood product transfusions, antiemetic medications, antiviral and antifungal medications, empiric antibiotics
Intervention MeSH terms: Cytarabine; Decitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: Phase II; decitabine; cytarabine; older patients; newly diagnosed; AML; Newly Diagnosed AML

Summary:

      Primary objective: To determine the efficacy of an induction regimen using decitabine as an
      epigenetic primer followed by cytarabine in the treatment of older patients with newly
      diagnosed Acute myeloid leukemia (AML).

      Primary endpoint:

      Complete remission rates

      Secondary objective: To determine the safety of an induction regimen of decitabine followed
      by cytarabine in the treatment of older patients with newly diagnosed AML, evaluate survival
      and identify potential predictive factors for response to treatment

      Secondary endpoints:

        -  Treatment related toxicities

        -  4 and 8 week mortality

        -  Overall survival

        -  Relapse-free survival

        -  Predictive factors for response to treatment

        -  Quality of Life measures including self reported symptoms and assessment of sleep
           patterns

      Treatment administration

      Induction therapy Eligible patients will be treated with induction therapy (decitabine +
      cytarabine) at the University of Pittsburgh Cancer Center inpatient leukemia service at
      Shadyside Hospital. Patients will receive decitabine 20mg/m2 in 100mL normal saline (NS)
      intravenously (IV) over 1 hour daily for five days, followed by cytarabine 100mg/m2 in 1000
      mL normal saline (NS) as a continuous IV infusion over 24 hours for 5 days. Treatment should
      be discontinued or delayed for any of the following during the treatment period: a rise in
      serum creatinine > 2x patient baseline or upper limit of normal (whichever is higher) unless
      there is an identifiable reversible etiology, or ALT, AST or total bilirubin > 5x upper limit
      of normal, and should be held until resolution below these parameters. There are no
      parameters for dose reduction.

      Patients who have persistent disease on post-treatment bone marrow aspirate and biopsy, will
      undergo a repeat cycle of induction with decitabine followed by cytarabine as outlined above.

      Supportive care including blood product transfusions, antiemetic medications antiviral and
      antifungal medications, or empiric antibiotics may be used at the clinical discretion of the
      provider.

      Maintenance therapy Patients in complete response (CR) will proceed to decitabine maintenance
      therapy, where each treatment will be decitabine 20mg/m2 in 100mL normal saline (NS)
      intravenously (IV) over 1 hour daily for five days administered in the outpatient setting.
      Maintenance treatments will be continued until disease relapse. Maintenance treatments can be
      administered as an outpatient at the Hillman Cancer Center, or at a University of Pittsburgh
      Medical Center (UPMC) facility that is able to administer chemotherapy under the supervision
      of an Oncologist

      Evaluations during maintenance Phase:

      During maintenance therapy, complete blood count (CBC) w/ diff/platelets, CMP (Na, K, Cl,
      carbon dioxide (CO2), glucose, blood urea nitrogen (BUN), Cr, Ca, Total Protein, Albumin,
      AST, ALT, Alk Phos, Total Bilirubin) will be checked each cycle on day 14 [+/- 4 days].

      Within 7 days of start of new cycle, study visits will include physical exam, adverse events
      assessment, CBC and comprehensive metabolic panel (CMP).

      Maintenance cycles will be 28 days [+/- 7 days]. Cycles can be held up to 4 weeks [28 days].
      For start of new cycle, any grade 3 or 4 non-hematologic toxicity possibly, probably or
      definitely related to decitabine therapy must resolve to grade 2 or baseline.

      In addition the following lab parameters must be met to start a new cycle of maintenance:

      Absolute Neutrophil Count (ANC) > or = 1000/mm3 Platelets >/= 50,000/mm3 AST or ALT < 2 x
      Uppler Limit of Normal (ULN) Total billirubin < 2 x ULN Serum creatinine < 2x patient
      baseline or upper limit of normal (whichever is higher)

      [If lab parameters are not met for start of cycle, these labs will be checked a minimum of
      once per week]. If start of new cycle is held for more than 4 weeks [28 days], the subject
      will be off treatment.

      Other reasons for delay in treatment should be discussed with the Principal Investigator.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 70, or age ≥ 60 ineligible for treatment with standard induction chemotherapy
             (based on physician discretion or patient refusal), with a new diagnosis of AML based
             on World Health Organization Classification.

          2. Eastern Cooperative Oncology Group Performance Status of 0-2

          3. Cardiac ejection fraction ≥45%

          4. Males are eligible to enter and participate in the study if they have either had a
             prior vasectomy or agree to avoid sexual activity or use adequate contraception from
             screening through two months post the last dose of decitabine

        Exclusion Criteria:

          1. Patients with acute promyelocytic leukemia

          2. Life expectancy ≤3 months

          3. Prior use of any hypomethylating agent or cytarabine

          4. Uncontrolled, life-threatening infection that is not responding to antimicrobial
             therapy

          5. Serum creatinine > 2x upper limit of normal

          6. Aspartate aminotransferase (AST),alanine aminotransferase (ALT), or total bilirubin >
             5x upper limit of normal

          7. History of psychiatric disorder which may compromise compliance with the protocol or
             which does not allow for appropriate informed consent

          8. Patient may not be receiving any other antineoplastic agents (hydroxyurea is allowed)

          9. Concurrent malignancy. Exception: Subjects who have been disease-free for 5 years, or
             subjects with a history of completely resected non-melanoma skin cancer or
             successfully treated in situ carcinoma are eligible. Subjects with second malignancies
             that are indolent or definitively treated may be enrolled.

         10. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
             respiratory, hepatic, renal, or cardiac disease).