Lirilumab and Azacitidine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia
Condition: Acute Biphenotypic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes
Intervention: Azacitidine; Lirilumab
Intervention description: Given SC or IV; Given IV
Intervention MeSH terms: Azacitidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase IB, lead-in/II to determine MTD
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects lirilumab and azacitidine and to see how well
      they work in treating patients with acute myeloid leukemia that has not responded to
      treatment or has returned after a period of improvement. Monoclonal antibodies, such as
      lirilumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in
      chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells,
      either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Giving lirilumab with azacitidine may be an effective treatment for relapsed or
      refractory acute myeloid leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with AML or biphenotypic or bilineage leukemia who have failed at least one
             prior therapy; patients with AML should have failed prior therapy or have relapsed
             after prior therapy

          -  Patients should not be eligible or able to receive approved therapy of confirmed
             clinical benefit in this patient population

          -  Patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML)
             who received therapy for the MDS or CMML and progress to AML are eligible at the time
             of diagnosis of AML regardless any prior therapy for AML; the World Health
             Organization (WHO) classification will be used for AML

          -  Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g.
             FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Total bilirubin =< 2 times upper limit of normal (x ULN) (=< 3 x ULN if considered to
             be due to leukemic involvement or Gilbert's syndrome)

          -  Aspartate aminotransferase or alanine aminotransferase =< 2.5 x ULN (=< 5.0 x ULN if
             considered to be due to leukemic involvement)

          -  Serum creatinine =< 2 x ULN or glomerular filtration rate (GFR) >= 50

          -  Patients must provide written informed consent

          -  In the absence of rapidly progressing disease, the interval from prior treatment to
             time of initiation of 5-azacytidine and lirilumab will be at least 2 weeks OR at least
             5 half-lives for cytotoxic/noncytotoxic agents; use of one dose of cytarabine (up to 2
             g/m^2) is allowed prior to the start of study therapy or hydroxyurea for patients with
             rapidly proliferative disease is allowed before the start of study therapy and while
             the patient is on active study treatment, as needed, for clinical benefit and after
             discussion with the principal investigator (PI); concurrent therapy for central
             nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease
             is permitted

          -  Females must be surgically or biologically sterile or postmenopausal (amenorrheic for
             at least 12 months) or if of childbearing potential, must have a negative serum or
             urine pregnancy test within 72 hours before the start of the treatment

          -  Women of childbearing potential must agree to use an adequate method of contraception
             during the study and until 30 days after the last treatment; males must be surgically
             or biologically sterile or agree to use an adequate method of contraception during the
             study until 30 days after the last treatment; women are considered post-menopausal and
             not of child bearing potential if they have had 12 months of natural (spontaneous)
             amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of
             vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without
             hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy
             alone, only when the reproductive status of the woman has been confirmed by follow up
             hormone level assessment is she considered not of child bearing potential

        Exclusion Criteria:

          -  Patients with known allergy or hypersensitivity to lirilumab, 5-azacytidine, or any of
             their components; patients who have previously been treated with lirilumab in
             combination with 5-azacytidine will be excluded

          -  Patients with a known history of severe interstitial lung disease or severe
             pneumonitis or active pneumonitis that is uncontrolled in the opinion of the treating
             physician

          -  Patients with a known history of any of the following autoimmune diseases are
             excluded: (a) patients with a history of inflammatory bowel disease (including Crohn's
             disease and ulcerative colitis) (b) patients with a history of rheumatoid arthritis,
             systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
             vasculitis [e.g., Wegener's granulomatosis])

          -  Patients with organ allografts (such as renal transplant) are excluded

          -  Patients with allogeneic stem cell transplantation within the last 6 months or
             patients with active graft-versus-host disease (GVHD) will be excluded

          -  Ongoing immunosuppressive therapy, including cyclosporine and tacrolimus; patients who
             are on high dose steroid; Note: Subjects may be using systemic corticosteroids (daily
             doses =< 10 mg of prednisone or equivalent) or topical or inhaled corticosteroids

          -  Patients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia

          -  Active and uncontrolled disease/(active uncontrolled infection, uncontrolled
             hypertension despite adequate medical therapy, active and uncontrolled congestive
             heart failure New York Heart Association [NYHA] class III/IV, clinically significant
             and uncontrolled arrhythmia) as judged by the treating physician

          -  Patients with active and uncontrolled human immunodeficiency virus (HIV) infection
             will be excluded; however, patients with well controlled HIV infection will be
             considered

          -  Patients known to be positive for hepatitis B by surface antigen expression; known to
             have active hepatitis C infection (positive by polymerase chain reaction or on
             antiviral therapy for hepatitis C within the last 6 months)

          -  Any other medical, psychological, or social condition that may interfere with study
             participation or compliance, or compromise patient safety in the opinion of the
             investigator

          -  Patients unwilling or unable to comply with the protocol

          -  Pregnant or breastfeeding

          -  Acute promyelocytic leukemia (APL)