A Study of Low-Dose Decitabine in Relapsed or Refractory Acute Lymphocytic Leukemia (ALL)

October 13, 2014 updated by: M.D. Anderson Cancer Center

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

The goal of this clinical research study is to find the safety of decitabine in patients with acute lymphocytic leukemia. Upon agreement of the patient, additional blood and bone marrow samples to be used to evaluate the effect of the treatment on leukemic cells. Also, with agreement of the patient, any leftover blood and bone marrow samples that are collected at the start of the study and during the regularly scheduled evaluations to be sent for research studies. The research studies will examine changes in the blood and bone marrow cells that might help explain the causes of leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 University of Texas MD Anderson Cancer Center (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, serum glutamate pyruvate transaminase (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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Decitabine
Decitabine administered intravenously (IV) over 1 hour at 10 mg/m2 daily x 5 days every other week.
Drug: Decitabine
Administered intravenously (IV) over 1 hour at 10 mg/m2 daily x 5 days every other week.
Other Names:
  • Dacogen
  • 5-Aza-2'-Deoxycytidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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).
Time Frame: 4 Years
4 Years
To determine the clinical activity of this schedule of decitabine in this patient population.
Time Frame: 4 Years
4 Years
To determine the safety and tolerability of decitabine in combination with hyperCVAD based chemotherapy in patients with relapsed or refractory ALL.
Time Frame: 4 Years
4 Years
To determine the clinical activity of this schedule of decitabine in combination with hyperCVAD in this patient population.
Time Frame: 4 Years
4 Years

Secondary Outcome Measures

Outcome Measure
Time Frame
To determine the effects of decitabine administration on DNA methylation and gene expression in this patient population.
Time Frame: 4 Years
4 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

Eisai Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (ACTUAL)

October 1, 2014

Study Completion (ACTUAL)

October 1, 2014

Study Registration Dates

First Submitted

July 6, 2006

First Submitted That Met QC Criteria

July 6, 2006

First Posted (ESTIMATE)

July 7, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

October 15, 2014

Last Update Submitted That Met QC Criteria

October 13, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2005-0895
  • NCI-2012-01369 (REGISTRY: NCI CTRP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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