Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory AML and MDS
Condition: Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts
Intervention: decitabine; idarubicin; cytarabine
Intervention description: Given IV; Given IV; Given IV
Intervention MeSH terms: Cytarabine; Decitabine; Azacitidine; Idarubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The goals of this study are to learn about the effectiveness, the side-effects, if waiting to
      give the idarubicin and cytarabine may change the side effects or effectiveness, and to
      identify factors to predict for responses to this therapy. The trial will examine combination
      of three chemotherapy drugs. These drugs are decitabine, idarubicin, and cytarabine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent

          -  All patients except those with acute promyelocytic leukemia (APL) who have
             morphological diagnosis of myelodysplastic syndromes (MDS) refractory anemia with
             excess blasts (RAEB)-II or AML by World Health Organization (WHO) diagnostic criteria
             and have either refractory or early relapsed disease; NOTE:

               -  Diagnosis of refractory or relapsed disease must be based on evaluation of a bone
                  marrow (BM) aspirate or peripheral blood (PB) flow cytometry; other standard MDS
                  and AML prognostic studies such as cytogenetics, flow, and molecular testing are
                  highly recommended prior to initiating DAC

               -  A previous BM evaluation or PB flow cytometry from an outside facility are
                  acceptable if the results have been deemed to be adequate for confirming the
                  diagnosis and staging by University of Washington (UW)/Seattle Cancer Care
                  Alliance (SSCA)/Fred Hutchinson Cancer Research Center (FHCRC) review

               -  A BM biopsy is not routinely required but should be obtained if the previous
                  evaluation is not deemed to be adequate for confirming diagnosis and staging by
                  UW/SCCA/FHCRC review

          -  Must have received at least one previous cycle of treatment for myelodysplastic
             syndrome (MDS) or AML and be either refractory as defined as not responded to this
             therapy or in early relapse as defined as developing recurrence of the disease within
             12 months of obtaining a CR

          -  May have previously received demethylating agents (e.g., DAC, 5-azacytidine [5AZA]) or
             histone deacetylases (e.g., suberoylanilide hydroxamic acid) for their MDS or AML if
             these demethylating agents were not used in combination with systemic anthracycline
             and ARAC chemotherapy

          -  May have received hematopoietic growth factors, thalidomide/lenalidomide, signal
             transduction inhibitors, or low dose cytarabine (=< 20 mg/m2/day)

          -  May not have received any therapy for their MDS or AML other than hydroxyurea or
             leukapheresis for at least 14 days prior to start of the first dose of DAC; all
             non-hematologic toxicities must have resolved to < grade 2

          -  Must have a "simplified" treatment-related mortality (TRM) score =< 9.2

          -  Females of childbearing potential must have a negative pregnancy test prior to
             initiation of the protocol therapy; females are considered not of child bearing
             potential if they are surgically sterile (they have undergone a hysterectomy,
             bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal

          -  Females of childbearing potential and males must be willing to use an effective method
             of contraception (hormonal or barrier method of birth control; abstinence) from the
             time consent is signed until 12 weeks after treatment discontinuation

          -  Patients with an active or history of other malignancies are eligible, if their
             projected overall survival for that malignancy is at least 6 months

          -  Prior hormonal therapy such as aromatase inhibitors, selective estrogen receptor
             modulators, estrogen receptor down-regulators, luteinizing hormone-releasing hormone
             (LHRH) agonists and antagonists, and anti-androgens, must be completed at least 30
             days prior to initiation of protocol therapy and must remain off hormonal therapy
             until the patient has finished chemotherapy for their MDS-RAEBII or AML

          -  Direct bilirubin =< 2.5 mg/dL (assessed within 14 days prior to registration) unless
             elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or
             hemolysis

          -  No known hypersensitivity to decitabine (DAC), aracytidine triphosphate (ARAC), or
             idarubicin hydrochloride (IDA)

          -  No clinical evidence of central nervous system (CNS) involvement with leukemia, unless
             a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid
             (CSF)

          -  No prior positive test for the human immunodeficiency virus (HIV)

          -  No uncontrolled systemic infection

        Exclusion Criteria:

          -  Previous therapy with demethylating agents (e.g., DAC, 5AZA, etc.) or histone
             deacetylases (e.g., suberoylanilide hydroxamic acid, etc.) that was combined with
             daunorubicin (DNR) or IDA and ARAC

          -  Patients with acute promyelocytic leukemia (APL)

          -  Known hypersensitivity to DAC, ARAC, or IDA

          -  Clinical evidence of CNS involvement with leukemia, unless a lumbar puncture confirms
             the absence of leukemic blasts in the CSF

          -  Prior positive test for HIV

          -  Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as
             exhibiting ongoing signs/symptoms related to the infection and without improvement,
             despite appropriate antibiotics or other treatment)

          -  A "simplified" TRM score > 9.2

          -  Bilirubin > 2.5 mg/dl (assessed within 14 days prior to registration), unless
             elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or
             hemolysis

          -  Patients who have a projected overall survival < 6 months due to malignancies other
             than MDS or AML

          -  Documented symptomatic congestive heart failure or a documented left ventricular
             ejection fraction < 40% assessed by multigated acquisition (MUGA), echocardiography,
             or heart catheterization within 21 days prior to start of decitabine