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

June 3, 2013 updated by: National Cancer Institute (NCI)

A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

42

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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
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
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
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Kristie Blum, Ohio State University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Primary Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

May 3, 2005

First Submitted That Met QC Criteria

May 3, 2005

First Posted (Estimate)

May 4, 2005

Study Record Updates

Last Update Posted (Estimate)

June 4, 2013

Last Update Submitted That Met QC Criteria

June 3, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-01465
  • U01CA076576 (U.S. NIH Grant/Contract)
  • 0475
  • CDR0000426523
  • OSU-0475
  • NCI-6997
  • OSU-2004C0119

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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