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Phase I Study of Low Dose 5-Aza-2'-Deoxycytidine Administered Daily for 5 Days Every Other Week for Patients With Relapsed or Refractory Acute Lymphocytic Leukemia

Phase 1
Open (Enrolling)
Acute Lymphocytic Leukemia

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Trial Information

Phase I Study of Low Dose 5-Aza-2'-Deoxycytidine Administered Daily for 5 Days Every Other Week for Patients With Relapsed or Refractory Acute Lymphocytic Leukemia

Decitabine is a potent hypomethylating agent with clinical activity in myelodysplastic
syndromes (MDS), and acute and chronic myelogenous leukemia (CML). In vitro, decitabine
induces loss of cell viability and apoptosis in ALL derived cell lines with known DNA
methylation alterations. Exposure of these cell lines to decitabine results in
hypomethylation and reactivation of putative tumor suppressor genes, an effect that is
thought to have a role in the antineoplastic activity of decitabine.

Aberrant DNA methylation of multiple promoter CpG islands is frequently observed in patients
with ALL both at initial presentation and at the time of relapse. Indeed these methylation
marks are stable in over 70% of patients with ALL at the time of relapse. Importantly,
methylation of specific molecular pathways has been associated with an extremely poor
prognosis in patients with ALL. For instance, data from our laboratory has identified
methylation, and silencing, of a cell cycle pathway composed of p73 and the cyclin dependent
kinase inhibitors p57KIP2 and p15, as a marker of poor prognosis in patients with
Philadelphia chromosome (Ph) negative disease. These results have been corroborated at the
protein level: expression of p57KIP2 and or p15/p73 has been associated with a better
prognosis. Finally, although the global methylation patterns observed in children with ALL,
that overall have an excellent prognosis, do not seem to differ with those of older patients
with the same genetic characteristics, methylation of prognostically significant pathways,
such as P73/P15/P57KIP2 are remarkably lower in the younger patients. Finally, introduction
of p57KIP2 in methylated/silenced ALL cell lines results in cell cycle arrest and induction
of apoptosis.

All these data indicates that aberrant methylation has a role in the clinical behavior of
patients with ALL and that its reversal may result in clinical benefit.

Inclusion Criteria:

1. Patients with refractory or relapsed acute lymphocytic leukemia (ALL).

2. Signed informed consent indicating that patients are aware of the investigational
nature of this study in keeping with the policies of UTMDACC.

3. Patients of any age are eligible.

4. Patients must have been off chemotherapy for 1 week prior to entering this study and
recovered from the toxic effects (< grade 2) of that therapy, unless there is
evidence of rapidly progressive disease. Use of high dose steroids with dexamethasone
is allowed during the first 2 courses of therapy. Imatinib mesylate (Gleevec) must be
stopped 1 week prior to entering this study.

5. Adequate liver function (bilirubin of < 3 mg/dL, SGPT < 5 x ULN) and renal function
(creatinine < 3mg/dL) unless proven to be related to disease infiltration.

6. Women of childbearing potential must practice contraception. Child bearing potential
defined as not post-menopausal for 12 months or no previous surgical sterilization.
Men and women must continue birth control for the duration of the trial.

Exclusion Criteria:

1) Nursing and pregnant females are excluded.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the safety and tolerability of 5-aza-2'-deoxycytidine (decitabine) administered daily for 5 days every other week in patients with relapsed or refractory acute lymphocytic leukemia (ALL).

Outcome Time Frame:

4 Years

Safety Issue:


Principal Investigator

Guillermo Garcia-Manero, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2006

Completion Date:

July 2014

Related Keywords:

  • Acute Lymphocytic Leukemia
  • Hypomethylating agent
  • Chemotherapy
  • Relapsed or refractory ALL
  • Acute Lymphocytic Leukemia (ALL)
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma



UT MD Anderson Cancer Center Houston, Texas  77030