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

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	Eisai Inc.
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00349596

Purpose

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.

Condition	Intervention	Phase
Acute Lymphocytic Leukemia	Drug: Decitabine	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Acute Lymphocytic Leukemia Cancer Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Azacitidine Deoxycytidine 5-Aza-2'-deoxycytidine

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
To determine the clinical activity of this schedule of decitabine in this patient population. [ Time Frame: 4 Years ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
To determine the clinical activity of this schedule of decitabine in combination with hyperCVAD in this patient population. [ Time Frame: 4 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the effects of decitabine administration on DNA methylation and gene expression in this patient population. [ Time Frame: 4 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	July 2006
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Decitabine	Drug: Decitabine Administered intravenously (IV) over 1 hour at 10 mg/m2 daily x 5 days every other week. Other Names: 5-Aza-2'-Deoxycytidine Dacogen

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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with refractory or relapsed acute lymphocytic leukemia (ALL).
Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of UTMDACC.
Patients of any age are eligible.
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.
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.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00349596

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Eisai Inc.

Investigators

Principal Investigator:

Guillermo Garcia-Manero, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

M.D. Anderson's website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00349596 History of Changes
Other Study ID Numbers:	2005-0895
Study First Received:	July 6, 2006
Last Updated:	January 13, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Hypomethylating agent
Chemotherapy
Relapsed or refractory ALL
Acute Lymphocytic Leukemia (ALL)

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

Decitabine
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012