Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Decitabine With or Without Valproic Acid in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00109824
First received: May 3, 2005
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Valproic acid may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine together with valproic acid may be an effective treatment for non-Hodgkin's lymphoma. This phase I trial is studying the side effects and best dose of decitabine and valproic acid in treating patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma.


Condition Intervention Phase
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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Toxicities of single agent decitabine alone and in combination with valproic acid assessed using CTCAE v3.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 42
Study Start Date: March 2006
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Drug: decitabine
Given IV
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Drug: valproic acid
Given PO
Other Names:
  • Alti-Valproic
  • Depakene
  • Novo-Valproic
  • VA
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
    • Transformed NHL* arising from a previously diagnosed low-grade lymphoma, including any of the following:

      • Follicular lymphoma
      • Small lymphocytic lymphoma
      • Chronic lymphocytic leukemia
  • 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)
  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: NCT00109824

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Kristie Blum Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00109824     History of Changes
Other Study ID Numbers: NCI-2012-01465, 0475, CDR0000426523, OSU-0475, NCI-6997, OSU-2004C0119, U01CA076576
Study First Received: May 3, 2005
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
DNA Virus Infections
Epstein-Barr Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, B-Cell
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Experimental
Tumor Virus Infections
Virus Diseases
Decitabine
Valproic Acid
Anticonvulsants
Antimanic Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
GABA Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 27, 2014