Decitabine and Gemtuzumab Ozogamicin in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (H-R MDS)
Condition: Acute Myelogenous Leukemia; Myelodysplastic Syndrome
MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Syndrome
Intervention: Decitabine; Gemtuzumab ozogamicin
Intervention description: Decitabine 20 mg/m^2 IV over 1-1/2 hours daily for 5 days.; Gemtuzumab ozogamicin 3 mg/m^2 IV on day 5.
Intervention MeSH terms: Decitabine; Gemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Acute Myelogenous Leukemia; High-Risk Myelodysplastic Syndrome; AML; MDS; Leukemia; Decitabine; Gemtuzumab Ozogamicin; Dacogen; Mylotarg

Summary:

      The goal of this clinical research study is to learn if 5-aza-2 deoxycytidine (decitabine)
      given in combination with Mylotarg (gemtuzumab ozogamicin) can help to control Acute myeloid
      leukemia (AML), high-risk myelodysplastic syndromes (MDS) or Myelofibrosis (MF). The safety
      of this drug combination will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Understand and voluntarily sign an informed consent form.

          2. Age >/= to 16 years at the time of signing the informed consent form.

          3. Diagnosis of AML [other than acute promyelocytic leukemia (APL)] with
             refractory/relapsed disease. Patients with newly diagnosed AML will be eligible if not
             a candidate for intensive chemotherapy. Patients with high-risk (intermediate-2 or
             high by International Prognostic Scoring System (IPSS) or >/= 10% blasts) MDS will
             also be eligible. All non-hematological toxicity of previous cancer therapy should
             have resolved to </= grade 1 (except alopecia or other toxicities not involving major
             organs).

          4. Eastern Cooperative Oncology Group (ECOG) performance status of </=3 at study entry.

          5. Laboratory test results within these ranges (unless due to leukemia): Serum creatinine
             </= 2 mg/dL Total bilirubin </= 2 mg/dL aspartate aminotransferase (AST) (SGOT) and/or
             alanine aminotransferase (ALT) (SGPT) </= 2.5 * upper limit of normal (ULN) or </= 5 *
             ULN if related to disease

          6. Women of childbearing potential (WCBP) must have a negative urine pregnancy test
             within 7 days and must either commit to continued abstinence from heterosexual
             intercourse or adopting at least one highly effective method of contraception. These
             methods include intra-uterine device, tubal ligation, partner's vasectomy, hormonal
             birth control pills. Men must agree not to father a child and agree to use a condom if
             his partner is of child bearing potential.

          7. Active participants of the similar Protocol 2007-0882 (preceding study of decitabine
             and Mylotarg) are eligible to roll-over to this protocol without meeting the inclusion
             or exclusion criteria for this study.

          8. For patients with MF only: Diagnosis of MF requiring therapy, including those
             previously treated by MF-directed therapy and relapsed or refractory; or if newly
             diagnosed then with intermediate or high risk according to Lille scoring system
             (adverse prognostic factors are: hemoglobin (Hb) < 10 g/dl, White blood cells (WBC) <
             4 or > 30 * 10^9/L; risk group: 0 = low, 1 = intermediate, 2 = high), or with
             symptomatic splenomegaly (>/=10cm below left mid-costal margin).

          9. For patients with MF only: Performance status 0-2 (Zubrod).

         10. For patients with MF only: Signed informed consent.

         11. For patients with MF only: Patients must have been off MF-directed therapy for 2 weeks
             prior to entering this study and have recovered from the toxic effects (grade 0-1) of
             that therapy. Patients are allowed to enter the study if on stable dose, for at least
             1 months, of anagrelide (to control high platelets) or hydroxyurea (to control high
             WBC or enlarging spleen), or on stable dose, for at least 2 months, of erythropoietin
             (for significant anemia).

         12. For patients with MF only: Serum bilirubin levels </= 2 times the upper limit of the
             normal range for the laboratory (ULN). Higher levels are acceptable if these can be
             attributed to active hemolysis or ineffective erythropoiesis, as judged by treating
             physician.

         13. For patients with MF only: Serum glutamic-pyruvic transaminase (SGPT) (alanine
             aminotransferase [ALT]) levels </= 2* ULN, unless related to the MF, as judged by
             treating physician.

         14. For patients with MF only: Serum creatinine levels </= 2* ULN.

         15. For patients with MF only: Women of childbearing potential must have a negative serum
             pregnancy test prior to treatment and should be advised to avoid becoming pregnant.
             Men must be advised to not father a child while receiving treatment. Both women of
             childbearing potential and men must practice effective methods of contraception (those
             generally accepted as standard of care measures).

         16. For patients with MF only: Age > 18 years.

        Exclusion Criteria:

          1. Pregnant or breastfeeding females.

          2. Any condition, including the presence of laboratory abnormalities, which places the
             patient at unacceptable risk.

          3. Use of any other experimental drug or therapy for leukemia within 14 days unless there
             is clear evidence of rapid disease progression. Use of hydrea to control proliferative
             disease will be allowed prior to starting therapy on study and for up to 7 days each
             during cycle 1-3 (Maximum daily dose of 7 gm).

          4. For patients with MF only: Nursing and pregnant females. Should a woman become
             pregnant or suspect she is pregnant while participating in this study, she should
             inform her treating physician immediately.

          5. For patients with MF only: Uncontrolled intercurrent illness including, but not
             limited to, uncontrolled active infection, symptomatic congestive heart failure,
             unstable angina pectoris, or psychiatric illness/social situations that would limit
             compliance with study requirements.