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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
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE May 3, 2005
First Posted Date  ICMJE May 4, 2005
Last Update Posted Date June 4, 2013
Study Start Date  ICMJE March 2006
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2012)
  • 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 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00109824 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Decitabine With or Without Valproic Acid in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title  ICMJE A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Mantle Cell Lymphoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Other: pharmacological study
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Drug: decitabine
    • Drug: valproic acid
    • Other: pharmacological study
    • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 8, 2006)
42
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00109824
Other Study ID Numbers  ICMJE NCI-2012-01465
0475
CDR0000426523
OSU-0475
NCI-6997
OSU-2004C0119
U01CA076576 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kristie Blum Ohio State University
PRS Account National Cancer Institute (NCI)
Verification Date June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP