Azacytidine Prior to in Vivo T-cell Depleted Allo Stem Cell Transplant for Patients With Myeloid Malignancies in CR
Condition: Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes
MeSH terms: Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes
Intervention: 5-Azacytidine; Fludarabine; Melphalan; Alemtuzumab; Total Body Irradiation
Intervention description: Patients will be given a five day course of subcutaneous 5-azacytidine followed by a reduced intensity conditioning regimen of fludarabine and melphalan with or without total body irradiation prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated HLA matched donor. 5-Azacytidine 75 mg/m2 subcutaneously daily at the same time on days -11, -10, -9,
-8 and -7. This will be administered on an outpatient basis if possible.; Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Fludarabine will be given at 40 mg/m2 intravenously daily at the same time over 30 minutes on days -6,-5,-4,-3.; Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Melphalan will be given at 140 mg/m2 IV on day -3.; Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Alemtuzumab will be given at 30 mg subcutaneously on Days -4 and -2 for unrelated donors, and Day -2 for related donors.; Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Total Body Irradiation (TBI) will be given at 2 doses of 200 cGy each on one day of the conditioning regimen (between days -6 and -3).
Intervention MeSH terms: Fludarabine; Azacitidine; Melphalan; Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether 5-Azacytidine priming before the
      conditioning regimen for subjects receiving a hematopoietic stem cell transplant is an
      effective treatment for high risk myeloid malignancies in complete remission (CR).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed acute myeloid leukemia
             (AML) or myelodysplastic syndrome (MDS) as specified below:

               1. Acute myeloid leukemia with poor risk cytogenetics in complete morphologic
                  remission. These include: del (5q)/-5, del (7q)/-7, abn 3q, 9q, 11q, 20q, 21q,
                  17p, t(6;9), t(9;22) or complex karyotypes (≥ 3 unrelated abnormalities); or

               2. Acute myeloid leukemia with either Flt-3, TET-2, p53, DNMT3A, or ASXL1 mutation,
                  mutations of genes involved in the chromatin/spliceosome category (EZH2, SRSF2,
                  U2AF1, ZRSR2), BCOR, and RUNX1, as well as MLL rearrangement, EVI1 overexpression
                  in complete morphologic remission; or

               3. Acute myeloid leukemia with a white blood cell count of greater than or equal to
                  50,000/mcL at presentation in first complete morphologic remission; or

               4. Acute myeloid leukemia in first complete morphologic remission, having required
                  more than one course of induction chemotherapy to attain remission status; or

               5. Acute myeloid leukemia, all types, excluding M3 (Promyelocytic leukemia) in
                  second or higher complete morphologic remission; or

               6. Myelodysplastic syndromes (intermediate-2, high risk and chronic myelomonocytic
                  leukemia (CMML) with bone marrow blasts <5%); or

               7. Secondary acute myeloid leukemia on the basis of prior MDS or prior
                  myeloproliferative neoplasm (MPN) in complete morphologic remission

          -  Life expectancy not severely limited by concomitant disease

          -  Karnofsky Performance Score greater than or equal to 70%.

          -  Adequate organ function as defined below:

        Serum Bilirubin:<2.0 mg/dL; Alanine Aminotransferase (ALT) (SGPT): <3 x upper limit of
        normal; Creatinine Clearance:>60 mL/min (eGFR as estimated by the modified Modification of
        Diet in Renal Disease Study (MDRD) equation)

        - Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Evidence of chronic active hepatitis or cirrhosis

          -  HIV infection

          -  Uncontrolled illness including, but not limited to, ongoing or active infection,
             symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
             psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Pregnant and lactating women are excluded from the study because the risks to an
             unborn fetus or potential risks in nursing infants are unknown.

          -  There are no prior therapies or concomitant medications that would render the patients
             ineligible