Phase I, Dose Escalation Study of Decitabine
Condition: Leukemia, Lymphoblastic, Acute; Leukemia, Myeloid Acute; Hematopoetic Myelodysplasia
MeSH terms: Leukemia; Leukemia, Myeloid; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 1

Summary: 
      Decitabine is a hypomethylating agent that has shown significant anti-leukemic effect in
      Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukemia (AML). This study is based on
      the hypothesis that Decitabine delivered after allo-hematopoietic stem cell transplant (HSCT)
      in patients with leukemia will enhance disease control by the allogeneic immune system and
      lead to a longer disease free survival. The study is designed to provide safety data of
      low-dosing in the post-transplant setting.
    

Detailed description: 
      Decitabine is a hypomethylating agent with significant anti-leukemic effect in MDS and AML.
      Additionally, aberrant DNA methylation has been identified in high risk childhood ALL, and
      therefore, DNA hypomethylating agents, such as decitabine, have been identified as
      therapeutic agents. Moreover, decitabine has immunomodulatory effects by enhancement of class
      I human leukocyte antigen (HLA) antigen expression on cancer cells, which increases their
      susceptibility to immune surveillance mechanisms, such as graft-versus-leukemia effect of
      donor cells in allogeneic transplantation and by augmentation of natural killer (NK), T and B
      lymphocyte reactivity. We hypothesize that decitabine delivered after allo-HSCT in patients
      with leukemia will enhance disease control by the allogeneic immune system and lead to a
      longer disease free survival. However, a safety study is needed to determine appropriate
      decitabine dosing in the post-transplant period. Low doses of decitabine are likely better
      tolerated in the post-transplant setting given risks of myelosuppression. In addition, when
      administered at lower doses, decitabine's hypomethylation effects are more pronounced in
      relation to its pyrimidine analog cytotoxic effects. In this study low doses of decitabine
      will be administered beginning 6 weeks to 100 days post-transplant. Measures of gene
      methylation and immune reconstitution will be conducted to define biologically active doses.
      Results from this trial will provide new clinical data regarding the effects of decitabine on
      gene methylation and immunoreactivity, will establish a maximally tolerated dose in the
      post-transplant setting, will define biologically active doses, and will serve as a basis for
      future efficacy trials.
    

Intervention name(s): Decitabine
Intervention type(s): Drug
Intervention description(s): Dose escalation starting at 5 mg, and increasing by 2.5 mg to a Dose Level of 12.5 mg qd x 3 days.
Other intervention name(s): Decitabine, Dacogen
Intervention MeSH terms: Decitabine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Relapse; Autologous stem cell transplant