NCT00079378

Brief Summary

This phase I trial is studying the side effects and best dose of decitabine and valproic acid in treating patients with refractory or relapsed acute myeloid leukemia or previously treated chronic lymphocytic leukemia or small lymphocytic leukemia. Drugs used in chemotherapy, such as decitabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Valproic acid may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Combining decitabine with valproic acid may kill more cancer cells.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
84

participants targeted

Target at P75+ for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2004

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

March 8, 2004

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 10, 2004

Completed
7.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2011

Completed
Last Updated

September 30, 2013

Status Verified

September 1, 2013

Enrollment Period

7.2 years

First QC Date

March 8, 2004

Last Update Submit

September 27, 2013

Conditions

Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult Acute Myeloid Leukemia With Del(5q)Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)Recurrent Adult Acute Myeloid LeukemiaRecurrent Small Lymphocytic LymphomaRefractory Chronic Lymphocytic LeukemiaUntreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (4)

  • MEPD of single agent decitabine

    10 days

  • MTD of the combination of valproic acid with the MEPD of decitabine

    Up to 21 days

  • MEPD of valproic acid in combination with decitabine

    Up to 29 days

  • Qualitative and quantitative toxicities of single agent decitabine alone and in combination with valproic acid in regard to organ specificity, time course, predictability, and reversibility

    Up to 24 months

Study Arms (1)

Treatment (decitabine, valproic acid)

EXPERIMENTAL

Patients receive decitabine IV over 1 hour on days 1-5 or 1-10. Treatment repeats every 28 days. Cohorts of 6 patients receive escalating doses of decitabine until the MEPD is determined. The MEPD is defined as the dose at which at least 5 of 6 patients meet gene methylation criteria and no more than 1 of 6 patients experiences DLT. Once the MEPD is determined, patients receive decitabine at that dose level administered as above and oral valproic acid three times daily on days 5-21. Treatment repeats every 28 days. Cohorts of 3-6 patients receive escalating doses of valproic acid until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. The MEPD of valproic acid is then determined using established gene methylation and toxicity criteria. Treatment continues for up to 24 months in the absence of disease progression or unacceptable toxicity.

Drug: decitabineDrug: valproic acidOther: pharmacological studyOther: laboratory biomarker analysis

Interventions

decitabineDRUG

Given IV

Also known as: 5-aza-dCyd, 5AZA, DAC
Treatment (decitabine, valproic acid)
valproic acidDRUG

Given orally

Also known as: Alti-Valproic, Depakene, Novo-Valproic, VA
Treatment (decitabine, valproic acid)
pharmacological studyOTHER

Correlative studies

Also known as: pharmacological studies
Treatment (decitabine, valproic acid)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (decitabine, valproic acid)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with AML (Stratum I) or CLL/SLL (Stratum II) will be enrolled
  • Patients in stratum I will have one of the following:
  • Primary refractory or relapsed (in 1 year or less) disease and not a candidate for potentially curative therapy
  • Untreated AML patients who are not candidates for chemotherapy
  • Patients in stratum I must have a normal WBC (=\< 10 x 10\^9/L) or a WBC =\< 40 x 10\^9/L that is stable for 1 week (this may be sustained with hydroxyurea prior to starting therapy and during the first 4 days of therapy if clinically indicated)
  • Patients in stratum II will have received at least one prior therapy for CLL/SLL that has included a purine analog; patients in stratum II with a history of severe autoimmune disease or requiring therapy with chronic corticosteroids or who have any other specific relative contraindications to receive a purine analog and, therefore, have received another form of therapy that include alkylating agents will be eligible to participate
  • Performance status - ECOG 0-2
  • At least 12 weeks life expectancy
  • Stratum II:
  • No uncontrolled autoimmune hemolytic anemia
  • No idiopathic thrombocytopenia purpura
  • Bilirubin =\< 1.5 mg/dL
  • ALT and AST =\< 2 times upper limit of normal
  • Creatinine =\< 2.0 mg/dL
  • No active infection requiring IV antibiotics
  • +19 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

  • Blum W, Klisovic RB, Hackanson B, Liu Z, Liu S, Devine H, Vukosavljevic T, Huynh L, Lozanski G, Kefauver C, Plass C, Devine SM, Heerema NA, Murgo A, Chan KK, Grever MR, Byrd JC, Marcucci G. Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. J Clin Oncol. 2007 Sep 1;25(25):3884-91. doi: 10.1200/JCO.2006.09.4169. Epub 2007 Aug 6.

    PMID: 17679729DERIVED

MeSH Terms

Conditions

Congenital AbnormalitiesLeukemia, Myeloid, AcuteLeukemia, Lymphocytic, Chronic, B-Cell

Interventions

DecitabineValproic Acid

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and AbnormalitiesLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, B-CellLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AzacitidineAza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesPentanoic AcidsValeratesAcids, AcyclicCarboxylic AcidsFatty Acids, VolatileFatty AcidsLipids

Study Officials

  • Kristie Blum

    Ohio State University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 8, 2004

First Posted

March 10, 2004

Study Start

February 1, 2004

Primary Completion

May 1, 2011

Last Updated

September 30, 2013

Record last verified: 2013-09

Locations

US(1)