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Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079378
First received: March 8, 2004
Last updated: September 27, 2013
Last verified: September 2013
History of Changes
  Purpose
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.

Condition Intervention Phase
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult 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 Leukemia
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Untreated Adult Acute Myeloid Leukemia
 Drug: decitabine
Drug: valproic acid
Other: pharmacological study
Other: laboratory biomarker analysis
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Selected Hematologic Malignancies

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MEPD of single agent decitabine [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
  • MTD of the combination of valproic acid with the MEPD of decitabine [ Time Frame: Up to 21 days ] [ Designated as safety issue: Yes ]
  • MEPD of valproic acid in combination with decitabine [ Time Frame: Up to 29 days ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]
Enrollment: 84
Study Start Date: February 2004
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (decitabine, valproic acid)

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: decitabine
Given IV
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Drug: valproic acid
Given orally
Other Names:
  • Alti-Valproic
  • Depakene
  • Novo-Valproic
  • VA
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility
Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • HIV negative
  • No other severe medical condition that would preclude study participation
  • No psychiatric condition that would preclude study compliance
  • No history of seizures
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • More than 14 days since prior chemotherapy (except hydroxyurea)
  • No prior FR901228 (depsipeptide) for step 2 of this study
  • No other concurrent chemotherapy
  • No concurrent corticosteroids for antiemetic therapy

  • No concurrent hormonal therapy except for the following:

    • Steroids for treatment of adrenal failure or septic shock
    • Insulin for diabetes
    • Tamoxifen or equivalent for breast cancer prevention or adjuvant therapy
    • Estrogens or progestins for gynecologic indications
  • More than 14 days since prior radiotherapy
  • No concurrent palliative radiotherapy
  • No concurrent anticonvulsant medication, including valproic acid
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00079378

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Kristie Blum Ohio State University
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00079378     History of Changes
Other Study ID Numbers: NCI-2012-01447  NCI-2012-01447  NCI-6236  OSU-2003C0094  CDR0000355412  0336  6236  R21CA110496  U01CA076576 
Study First Received: March 8, 2004
Last Updated: September 27, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Decitabine
Azacitidine
 Valproic Acid
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Anticonvulsants
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on September 29, 2016