Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
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ClinicalTrials.gov Identifier: NCT00079378 |
Recruitment Status :
Completed
First Posted : March 10, 2004
Last Update Posted : September 30, 2013
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Condition or disease | Intervention/treatment | 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 (Clinical Trial) |
Actual Enrollment : | 84 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Selected Hematologic Malignancies |
Study Start Date : | February 2004 |
Actual Primary Completion Date : | May 2011 |

Arm | Intervention/treatment |
---|---|
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:
Drug: valproic acid Given orally
Other Names:
Other: pharmacological study Correlative studies
Other Name: pharmacological studies Other: laboratory biomarker analysis Correlative studies |
- MEPD of single agent decitabine [ Time Frame: 10 days ]
- MTD of the combination of valproic acid with the MEPD of decitabine [ Time Frame: Up to 21 days ]
- MEPD of valproic acid in combination with decitabine [ Time Frame: 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 [ Time Frame: Up to 24 months ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
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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
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00079378
United States, Ohio | |
Ohio State University Medical Center | |
Columbus, Ohio, United States, 43210 |
Principal Investigator: | Kristie Blum | Ohio State University |
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00079378 |
Other Study ID Numbers: |
NCI-2012-01447 NCI-2012-01447 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) NCI-6236 OSU-2003C0094 CDR0000355412 0336 ( Other Identifier: Ohio State University Medical Center ) 6236 ( Other Identifier: CTEP ) R21CA110496 ( U.S. NIH Grant/Contract ) U01CA076576 ( U.S. NIH Grant/Contract ) |
First Posted: | March 10, 2004 Key Record Dates |
Last Update Posted: | September 30, 2013 |
Last Verified: | September 2013 |
Lymphoma Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Recurrence Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Disease Attributes Pathologic Processes |
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 |