Azacitidine and Lintuzumab in Treating Patients With Previously Untreated Myelodysplastic Syndromes
Condition: Leukemia; Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: lintuzumab; 5-azacytidine
Intervention description: Cycle 1 600mg as an IV infusion (flat dose for all), given on days 2, 7, 15, and 22. Subsequent Cycles (cycles to be repeated every 28 days) 600mg as an IV infusion, given every other week, twice during each cycle, including one dose given during AZA therapy. Doses should be given at least 12 days apart. By convention, dosing on days 7 and 22 of each cycle will be encouraged, but due to expected issues of patient convenience (time, travel, etc.), the study requirements are every other week, twice during each cycle, with one dose during AZA treatment.; 75mg/m2 IV/SC daily on days 1-7.
Intervention MeSH terms: Azacitidine; Lintuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: de novo myelodysplastic syndromes; secondary myelodysplastic syndromes; chronic myelomonocytic leukemia; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory anemia; refractory cytopenia with multilineage dysplasia

Summary:

      RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop
      the growth of cancer cells, either by killing the cells or by stopping them from dividing.
      Monoclonal antibodies, such as lintuzumab, can block cancer growth in different ways. Some
      block the ability of cancer cells to grow and spread. Others find cancer cells and help kill
      them or carry cancer-killing substances to them. Giving chemotherapy together with monoclonal
      antibodies may be a better way to block cancer growth.

      PURPOSE: This phase II trial is studying the side effects and how well giving azacitidine
      together with lintuzumab works in treating patients with previously untreated myelodysplastic
      syndromes.
    

Eligibility criteria:

        Eligibility Criteria:

          -  Age >18 with untreated MDS by FAB or WHO criteria (note: FAB criteria for MDS includes
             <29% blasts; FAB criteria includes CMML).

          -  Patients with therapy related disease (t-MDS).

          -  If the patient has co-morbid medical illness, life expectancy attributed to this must
             be greater than 6 months.

          -  Eastern Cooperative Oncology Group (ECOG) performance status <2.

          -  Must have adequate organ function as defined below:

               -  total bilirubin <2.0mg/dL

               -  AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

               -  creatinine <2.0mg/dL

               -  NYHA CHF(congestive heart failure)Class II or better

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence).

          -  Ability to understand and willingness to sign the written informed consent document.

          -  CD33 expression is required on at least 25% of left shifted dysplastic myeloid cells,
             including blasts. This testing will be done on bone marrow aspirate, but for patients
             whose CD33 expression in this cellular compartment cannot be ascertained, peripheral
             blood will be allowed to determine this.

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 6 months (for other cancers)
             prior to entering the study.

          -  Patients receiving any other investigational agents or patients that have received
             other investigational agents within 1 month of enrollment.

          -  Patients with active central nervous system disease or with granulocytic sarcoma as
             sole site of disease.

          -  Patients with history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to AZA or lintuzumab that are not easily managed are
             excluded. Patients with hypersensitivity to mannitol are excluded.

          -  Uncontrolled intercurrent illness including, but not limited to, symptomatic
             congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or
             psychiatric illness/social situations that would limit compliance with study
             requirements. As infection is a common feature of MDS, patients with active infection
             are permitted to enroll provided that the infection is under control. Myocardial
             infarction within 6 months prior to enrollment or has New York Heart Association
             (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled
             ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active
             conduction system abnormalities.

          -  Psychiatric conditions that prevent compliance with protocol or consent.

          -  Pregnant women or women who are breastfeeding are excluded from this study.

          -  HIV-positive patients on combination antiretroviral therapy are ineligible.

          -  Patients with serious medical or psychiatric illness likely to interfere with
             participation in this clinical study.

          -  Patients with serious medical or psychiatric illness likely to interfere with
             participation in this clinical study.

          -  Patients with baseline fibrinogen <100mg/dL, or those with clinically significant
             disseminated intravascular coagulation, are excluded.

          -  Patients who require ongoing therapeutic anticoagulation with warfarin, lovenox, or
             similar agent are excluded. This does not apply to patients on low dose prophylaxis
             therapy.

          -  Patients who require ongoing clopidogrel therapy are excluded. In cases where
             clopidogrel use at screening is subsequently discontinued due to ongoing or future
             risk of drug and treatment related cytopenias, such patients will be eligible.

          -  Patients with platelet <10,000/uL who are refractory to platelet transfusion are not
             eligible (must bump to at least >10,000/uL after transfusion)

          -  Patients who have previously received lenalidomide or thalidomide are excluded.