Azacitidine + Lenalidomide Combo in the Elderly With Previously Treated AML & High-Risk MDS
Condition: Leukemia; Acute Myeloid Leukemia (AML); Myelodysplastic Syndromes (MDS)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes
Intervention: Azacitidine; Lenalidomide
Intervention description: Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death; Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory activity.
Intervention MeSH terms: Lenalidomide; Azacitidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No

Summary:

      The purpose of the trial is to study how the elderly patients who have previously undergone
      treatment for acute myeloid leukemia and high-rRisk myelodysplastic syndromes, respond to a
      combined treatment with azacitidine and lenalidomide.
    

Eligibility criteria:

        Inclusion Criteria:

          -  acute myeloid leukemia (AML) (according to the WHO 2008 classification):

               -  De novo

               -  Secondary AML previously treated with demethylating agents for AML

               -  Secondary AML previously treated with demethylating agents for MDS

               -  Secondary AML previously treated with high dose lenalidomide for AML (≥ 25mg)

          -  High Risk MDS:

               -  Del (5q)

               -  Non-del (5q), previously-treated with lenalidomide.

               -  Novo or secondary HR-MDS previously treated with demethylating agents

          -  White blood cell (WBC) ≤ 10,000

          -  Age ≥ 60

          -  Not an immediate candidate for allogeneic stem cell transplantation

          -  Unwilling or unable to receive conventional chemotherapy

          -  Prior therapy:

               -  with single agent demethylator (5-Azacitidine or Decitabine)

               -  with Lenalidomide

          -  Eastern Cooperative Oncology Group performance status ≤ 2

          -  Life expectancy > 2 months

          -  All study participants must be registered into the mandatory RevAssist program

          -  Willing and able to comply with the requirements of RevAssist

          -  Females of childbearing potential (FCBP)† must have a negative serum or urine
             pregnancy test 10-14 days prior to study enrollment and again within 24 hours of
             prescribing lenalidomide

               -  Must commit to either continued abstinence from intercourse or begin two
                  acceptable methods of birth control, at least 28 days before she starts taking
                  lenalidomide.

               -  Must also agree to ongoing pregnancy testing.

          -  Men must agree to use a latex condom during sexual contact with a FCBP even if they
             have had a successful vasectomy.

          -  Willing and able to understand and voluntarily sign a written informed consent

          -  Able to adhere to the study visit schedule and other protocol requirements

        Exclusion Criteria:

          -  Patients with LR-MDS progressing to HR-MDS after low dose lenalidomide or 5-day
             azacitidine will not be eligible.

          -  History of intolerance to thalidomide

             -development of erythema nodosum while taking thalidomide or similar drugs

          -  Known or suspected hypersensitivity to azacitidine or mannitol

          -  Patients with advanced malignant hepatic tumors.

          -  Concomitant treatment with other anti-neoplastic agents, with the exception of
             hydroxyurea

          -  Previous participation on the VIREL study with the concomitant use of azacitidine plus
             lenalidomide.

          -  Anti-neoplastic treatment less than four weeks prior to enrollment, with the exception
             of hydroxyurea

          -  Use of any other experimental drug or therapy within 28 days of baseline

          -  Inability to swallow or absorb drug

          -  Active opportunistic infection or treatment for opportunistic infection within four
             weeks of first day of study drug dosing

          -  New York Heart Association Class III or IV heart failure

          -  Unstable angina pectoris

          -  Uncontrolled cardiac arrhythmia

          -  Uncontrolled psychiatric illness that would limit compliance with requirements

          -  Known HIV infection

          -  Pregnant

          -  Breast feeding

          -  Lactating females must agree not to breast feed while taking lenalidomide

          -  Other medical or psychiatric illness or organ dysfunction or laboratory abnormality

          -  Laboratory abnormalities:

               -  Either creatinine ≥ 1.5 mg / dL or creatinine clearance ≤ 50 mL / min

               -  Total bilirubin >1.5 x institutional ULN

               -  AST and ALT > 2.5 x institutional ULN