Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Azacitidine; Lenalidomide; Off Therapy
Intervention description: Enrolled patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone.; Beginning on day 8, patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28.; 2 weeks off therapy, then begin sequence again for 12 weeks.
Intervention MeSH terms: Lenalidomide; Azacitidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myeloid; Leukemia

Summary:

      The primary objective of this study is to determine the complete remission/complete remission
      with incomplete recovery of blood counts (CR/CRi) rate for relapsed and refractory acute
      myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  • World Health Organization (WHO)-confirmed AML, other than Acute Promyelocytic
             Leukemia (APL)

               -  Age >18 years

               -  White blood cell count (WBC) at initiation of treatment ≤ 10,000/L

                  o If WBC is > 10,000/L patients may be started on an appropriate dose of
                  hydroxyurea (to be determined by the investigators), until WBC < 10,000/L, at
                  which time the hydroxyurea will be discontinued for 12 hours prior to enrollment

               -  Relapsed or refractory (resistant) disease, as defined by standard criteria21:

                    -  Relapsed: Bone marrow blasts ≥5%; reappearance of blasts in the blood;
                       development of extramedullary disease

                    -  Refractory (resistant): Failure to achieve Complete Remission (CR) or
                       complete remission with incomplete recovery of blood counts (CRi) in
                       patients who survive ≥7 days following completion of initial treatment, with
                       evidence of persistent leukemia by blood and/or bone marrow examination

               -  Failure of at least one prior therapy

               -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (See Appendix D:
                  ECOG Performance Status Scale)

               -  Life expectancy > 2 months

               -  All study participants must be registered into the mandatory RevAssist® program,
                  and be willing and able to comply with the requirements of RevAssist® (RevAssist
                  is a restricted distribution program for receiving lenalidomide)

               -  Females of childbearing potential (FCBP)† must have a negative serum or urine
                  pregnancy test with a sensitivity of at least 50 million International Units per
                  milliliter (mIU/mL) 10 - 14 days prior to study enrollment and again within 24
                  hours of prescribing lenalidomide (prescriptions must be filled within 7 days)
                  and must either commit to continued abstinence from heterosexual intercourse or
                  begin two acceptable methods of birth control, one highly effective method and
                  one additional effective method at the same time, at least 28 days before she
                  starts taking lenalidomide. FCBP 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. See Appendix F: Risks of Fetal Exposure,
                  Pregnancy Testing Guidelines and Acceptable Birth Control Methods

               -  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:

          -  • Known or suspected hypersensitivity to azacitidine or mannitol

               -  Patients with advanced malignant hepatic tumors.

               -  Treatment less than four weeks prior to enrollment with other experimental
                  therapies or antineoplastic agents, with the exception of hydroxyurea

               -  Inability to swallow or absorb drug

               -  Prior treatment with lenalidomide for AML

               -  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

               -  Significant uncontrolled cardiac arrhythmias

               -  Uncontrolled psychiatric illness that would limit compliance with requirements

               -  Known Human immunodeficiency virus (HIV) infection

               -  Graft vs. host disease ≥ grade 2

               -  Relapse after allogeneic stem cell transplantation prior to post-transplant day
                  30

               -  Pregnant or breast feeding females; lactating females must agree not to breast
                  feed while taking lenalidomide

               -  Other medical or psychiatric illness or organ dysfunction or laboratory
                  abnormality which in the opinion of the investigator would compromise the
                  patient's safety or interfere with data interpretation

               -  Laboratory abnormalities:

                    -  Either creatinine >2.0 mg/dL or creatinine clearance <30 mL/min

                    -  Total bilirubin > 2 x institutional upper limit of normal (ULN) (unless
                       documented Gilbert's syndrome)

                    -  Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) > 3 x
                       institutional ULN