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

This study is not yet open for patient recruitment.

Sponsors and Collaborators: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: 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.

PURPOSE: 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 Treatment or Intervention Phase
recurrent adult Burkitt's lymphoma
recurrent adult diffuse large cell lymphoma
recurrent mantle cell lymphoma
 Drug: decitabine
 Drug: valproic acid
 Procedure: chemotherapy
 Procedure: enzyme inhibitor therapy
Phase I

MedlinePlus related topics:  Cancer;   Cancer Alternative Therapy;   Lymphoma;   Viral Infections

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I Study of Decitabine Alone or in Combination With Valproic Acid in Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin's Lymphoma

Further Study Details: 

OBJECTIVES: Primary

Secondary

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 treatment stages.

  • : Patients receive decitabine IV over 1 hour on days 1-10. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 6 patients receive escalating doses of decitabine until the minimally effective pharmacological dose (MEPD) is determined. The MEPD is defined as the dose at which an 80% decrease in DNMT1 protein level AND a 100% increase in re-expression of the methylated target genes (DAP-kinase, p15^INK4b, or p16^INK4a) occurs in 5 of 6 patients AND ≤ 1 of 6 patients experiences dose-limiting toxicity (DLT).
  • : Patients receive decitabine as in stage 1 and oral valproic acid three times daily on days 5-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of valproic acid in combination with the MEPD of decitabine (determined in stage 1) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. Once the MTD of valproic acid is determined, 6 patients are treated at the MTD and at 1 lower dose level to determine the MEPD of valproic acid in combination with decitabine. The MEPD of the combination is defined as the plasma level of valproic acid at which either an 80% of histone deacetylase (HDAC) enzyme inhibition OR a 100% increase in baseline H3 and H4 acetylation AND a 100% increase in re-expression of the methylated target genes (DAP-kinase, p15^INK4b, or p16^INK4a) occurs in 5 of 6 patients AND ≤ 1 of 6 patients experiences DLT.

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 above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

PATIENT CHARACTERISTICS: Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3*
  • Platelet count ≥ 75,000/mm^3* NOTE: *Unless related to lymphoma

Hepatic

  • AST and ALT ≤ 2.5 times upper limit of normal
  • Bilirubin ≤ 1.5 mg/dL

Renal

  • Creatinine ≤ 2.0 mg/dL

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other

  • 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 CONCURRENT THERAPY: Biologic therapy

Chemotherapy

  • At least 21 days since prior chemotherapy and recovered
  • No other concurrent chemotherapy unless it is used in the chronic daily setting for other medical conditions, including pulmonary, rheumatologic, or adrenal disorders

Endocrine therapy

  • No concurrent corticosteroids unless they are used in the chronic daily setting for other medical conditions, including pulmonary, rheumatologic, or adrenal disorders

Radiotherapy

  • At least 21 days since prior radiotherapy and recovered
  • No concurrent palliative radiotherapy

Surgery

  • Not specified

Other


Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier  NCT00109824


Study chairs or principal investigators

Kristie A. Blum, MD,  Study Chair,  Arthur G. James Cancer Hospital & Richard J. Solove Research Institute   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000426523; OSU-2004C0119; NCI-6997; OSU-0475; NCT00109824
Record last reviewed:  April 2005
Last Updated:  May 12, 2005
Record first received:  May 3, 2005
ClinicalTrials.gov Identifier:  NCT00109824
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-05-17


Source: ClinicalTrials.gov
Cache Date: May 18, 2005