Decitabine With or Without Valproic Acid in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
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ClinicalTrials.gov Identifier: NCT00109824 |
Recruitment Status :
Completed
First Posted : May 4, 2005
Last Update Posted : June 4, 2013
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Condition or disease | Intervention/treatment | Phase |
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Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Mantle Cell Lymphoma | Drug: decitabine Drug: valproic acid Other: pharmacological study Other: laboratory biomarker analysis | Phase 1 |
PRIMARY OBJECTIVES:
I. Determine the minimally effective pharmacological dose (MEPD) of single-agent decitabine in patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma.
II. Determine the maximum tolerated dose of valproic acid when administered with the MEPD of decitabine in these patients.
III. Determine the MEPD of valproic acid when administered with decitabine in these patients.
IV. Determine the toxic effects of decitabine alone and in combination with valproic acid in these patients.
SECONDARY OBJECTIVES:
I. Determine the response rate in patients treated with these drugs. II. Determine the pharmacokinetics of these drugs in these patients.
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 treatment stages.
STAGE 1: Patients receive decitabine IV over 1 hour on days 1-5 or 1-10. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
STAGE 2: Patients receive decitabine as in stage 1 and valproic acid orally (PO) thrice daily (TID) on days 5-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
For both stages, patients who achieve an objective response (complete response [CR], unconfirmed CR, or partial response) may discontinue study treatment and undergo stem cell transplantation, if eligible.
PROJECTED ACCRUAL: Approximately 18-42 patients (18 for stage 1 and 24 for stage 2) will be accrued for this study.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 42 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma |
Study Start Date : | March 2006 |
Actual Primary Completion Date : | March 2009 |

Arm | Intervention/treatment |
---|---|
Experimental: Arm I
Patients receive decitabine IV over 1 hour on days 1-5 or 1-10. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
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Other: pharmacological study
Correlative studies
Other Name: pharmacological studies Other: laboratory biomarker analysis Correlative studies |
Experimental: Arm II
Patients receive decitabine as in stage 1 and valproic acid PO TID on days 5-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
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Drug: decitabine
Given IV
Other Names:
Drug: valproic acid Given PO
Other Names:
Other: pharmacological study Correlative studies
Other Name: pharmacological studies Other: laboratory biomarker analysis Correlative studies |
- MEPD of single agent decitabine defined as the dose where an 80% decrease in DNMT1 protein level and a 100% increase in re-expression of the methylated target genes are noted in 5 of 6 patients, with DLT in less than or equal to 1 patient [ Time Frame: 28 days ]
- MTD of valproic acid in combination with the MEPD of decitabine defined as the dose level below that dose at which greater than or equal to 2 DLT are observed and that results in less than or equal to 1 DLT in 6 patients using CTCAE v3.0 [ Time Frame: 28 days ]
- MEPD of valproic acid and decitabine defined as the dose where an 80% decrease in DNMT1 protein level and a 100% increase in re-expression of the methylated target genes are noted in 5 of 6 patients, with DLT in less than or equal to 1 patient [ Time Frame: 28 days ]
- Toxicities of single agent decitabine alone and in combination with valproic acid assessed using CTCAE v3.0 [ Time Frame: Up to 3 years ]

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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:
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Histologically or cytologically confirmed aggressive B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes:
- Mantle cell lymphoma
- Diffuse large cell lymphoma
- Burkitt's lymphoma
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Transformed NHL* arising from a previously diagnosed low-grade lymphoma, including any of the following:
- Follicular lymphoma
- Small lymphocytic lymphoma
- Chronic lymphocytic leukemia
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Relapsed or refractory disease
- Relapsed or refractory disease must have occurred during the most recent prior therapy
- Has accessible tissue for biopsy OR evidence of ≥ 50% bone marrow involvement AND willing to undergo serial biopsy
- Not eligible for OR refused curative stem cell transplantation
- No active or untreated CNS lymphoma
- Performance status - ECOG 0-2
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 75,000/mm^3
- AST and ALT ≤ 2.5 times upper limit of normal
- Bilirubin ≤ 1.5 mg/dL
- Creatinine ≤ 2.0 mg/dL
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No known HIV positivity
- No ongoing or active infection
- No other uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
- Prior stem cell transplantation allowed
- Recovered from all prior biologic therapy-related toxicity
- Recovered from all prior chemotherapy-related toxicity
- No other concurrent chemotherapy unless it is used in the chronic daily setting for other medical conditions, including pulmonary, rheumatologic, or adrenal disorders
- No concurrent corticosteroids unless they are used in the chronic daily setting for other medical conditions, including pulmonary, rheumatologic, or adrenal disorders
- Recovered from all prior radiotherapy-related toxicity
- No concurrent palliative radiotherapy
- Recovered from all prior therapy-related toxicity
- No concurrent anticonvulsants, including valproic acid (except as used in this study)

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): NCT00109824
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: | NCT00109824 |
Other Study ID Numbers: |
NCI-2012-01465 0475 CDR0000426523 OSU-0475 NCI-6997 OSU-2004C0119 U01CA076576 ( U.S. NIH Grant/Contract ) |
First Posted: | May 4, 2005 Key Record Dates |
Last Update Posted: | June 4, 2013 |
Last Verified: | June 2013 |
Burkitt Lymphoma Lymphoma Lymphoma, Mantle-Cell Lymphoma, Large B-Cell, Diffuse Recurrence Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Disease Attributes Pathologic Processes Lymphoma, Non-Hodgkin Lymphoma, B-Cell |
Epstein-Barr Virus Infections Herpesviridae Infections DNA Virus Infections Virus Diseases Infections Tumor Virus Infections Decitabine Azacitidine Valproic Acid Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors Anticonvulsants |