Patient case: 13-year-old male with acute myeloid leukemia; genetic feature: FLT3

Clinical trial: Azacytidine Prior to in Vivo T-cell Depleted Allo Stem Cell Transplant for Patients With Myeloid Malignancies in CR

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).

Detailed description: This open label two-step phase II study is designed to determine the safety and efficacy of epigenetic priming with 5-Azacytidine immediately prior to reduced intensity conditioning for an in vivo T-cell depleted hematopoietic stem cell transplantation for high risk myeloid malignancies in complete remission (CR).
  Subjects will be given a five day course of subcutaneous 5-azacytidine, followed by a reduced intensity conditioning regimen of fludarabine and melphalan prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated HLA matched donor.
  The effect of 5-azacytidine on global gene methylation will be assessed. Evaluations for safety, in particular for graft failure, transplant related mortality and acute graft versus host disease will be made on a weekly basis. Efficacy, as defined by disease free survival, will be evaluated with a bone marrow biopsy at the standard time points, which are one-, three-, six-, and twelve-months after transplant and upon clinical suspicion within regular follow-up visits - weekly for the first 3 months, then biweekly for 3 months, then monthly until one-year post-SCT. Thereafter, unless otherwise dictated by the clinical scenario, the follow up visits will be every 3 months.

Eligibility: Inclusion Criteria:
  -  Patients must have histologically or cytologically confirmed AML or MDS as specified below:
  1. Acute myeloid leukemia with poor risk cytogenetics (1) in complete hematologic remission. These include: del (5q)/-5, del (7q)/-7, abn 3q, 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22) and complex karyotypes (≥ 3 unrelated abnormalities); or
  2. Acute myeloid leukemia with Flt-3 mutation in complete hematologic remission; or
  3. Acute myeloid leukemia, all types, excluding M3 (Promyelocytic leukemia) in second or higher hematologic remission; or
  4. Myelodysplastic syndromes (intermediate-2, high risk and CMML with bone marrow blasts <5%); or
  Secondary acute myeloid leukemia on the basis of prior MDS in hematologic remission
  -  Life expectancy not severely limited by concomitant disease
  -  ECOG performance status less than or equal to 2
  -  Adequate organ function as defined below:
  Serum Bilirubin:<2.0 mg/dL ALT (SGPT): <3X upper limit of normal Creatinine Clearance:>50 mL/min (eGFR as estimated by the modified 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

Relevance to patient case: not relevant