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Phenylbutyrate Plus Azacitidine in Treating Patients With Acute Myeloid Leukemia, Myelodysplasia, Non-Hodgkin's Lymphoma, Multiple Myeloma, Non-Small Cell Lung Cancer, or Prostate Cancer

This study has been completed.

Sponsors and Collaborators: Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006019
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of phenylbutyrate plus azacitidine in treating patients who have acute myeloid leukemia, myelodysplasia, non-Hodgkin's lymphoma, multiple myeloma, non-small cell lung cancer, or prostate cancer.


Condition Intervention Phase
Leukemia
Lung Cancer
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Prostate Cancer
Drug: azacitidine
Drug: sodium phenylbutyrate
Phase II

Genetics Home Reference related topics:   aceruloplasminemia    hemophilia   

MedlinePlus related topics:   Cancer    Leukemia, Adult Acute    Leukemia, Adult Chronic    Lung Cancer    Lymphoma    Multiple Myeloma    Prostate Cancer   

ChemIDplus related topics:   Azacitidine    Sodium phenylbutyrate   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Open Label
Official Title:   Pilot Study of Sodium Phenylbutyrate Plus Azacytidine

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

Study Start Date:   May 2000

Detailed Description:

OBJECTIVES:

  • Determine the ability of azacytidine in vivo to demethylate selected genes known to be transcriptionally repressed in patients with acute myeloid leukemia, myelodysplasia, non-Hodgkin's lymphoma, multiple myeloma, non-small cell lung cancer, or prostate cancer.
  • Determine the ability of phenylbutyrate plus azacytidine to induce transcription of target genes that are known to be repressed as a consequence of DNA methylation in these patients.
  • Determine the effect of this treatment regimen upon gene methylation and histone acetylation in target cells in these patients.
  • Determine the technical feasibility of serially monitoring transcriptional activity and methylation status of selected genes in vivo in these patients.
  • Determine the safety and potential antitumor efficacy of this treatment regimen in these patients.

OUTLINE: Patients receive azacytidine subcutaneously on days 1-7 and phenylbutyrate IV over 1-2 hours on days 8-12. Patients with acute myeloid leukemia who respond to therapy may receive a second course approximately 10 days after the end of the first. Subsequent courses in these patients, and all additional courses in all other patients, are repeated every 21 to 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 20 patients 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

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following neoplastic diseases:

    • Acute myeloid leukemia
    • Myelodysplasia
    • Low or intermediate grade non-Hodgkin's lymphoma
    • Multiple myeloma
    • Non-small cell lung cancer
    • Prostate cancer
  • Failed prior conventional therapy and no other known curative therapy exists
  • Patients with non-Hodgkin's lymphoma, non-small cell lung cancer, and prostate cancer must have tumor cells in bone marrow or malignant effusions that are accessible for bone marrow aspiration or paracentesis/thoracentesis NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • Patients without leukemia or myeloma:

    • WBC at least 2,500/mm^3
    • Platelet count at least 75,000/mm^3

Hepatic:

  • Bilirubin no greater than 2.5 mg/dL

Renal:

  • Creatinine no greater than 2.5 mg/dL

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 weeks after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • Patients without leukemia:

    • At least 3 weeks since prior cytotoxic chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Patients without leukemia:

    • At least 3 weeks since prior radiotherapy

Surgery:

  • Not specified
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006019

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center    
      New York, New York, United States, 10021

Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)

Investigators
Study Chair:     Peter Maslak, MD     Memorial Sloan-Kettering Cancer Center    
  More Information


Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   CDR0000068030, MSKCC-99060, NCI-T99-0091
First Received:   July 5, 2000
Last Updated:   July 23, 2008
ClinicalTrials.gov Identifier:   NCT00006019
Health Authority:   United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent non-small cell lung cancer  
refractory plasma cell neoplasm  
recurrent adult acute myeloid leukemia  
recurrent prostate cancer  
adult acute myeloblastic leukemia without maturation (M1)  
adult acute myeloblastic leukemia with maturation (M2)  
adult acute promyelocytic leukemia (M3)  
adult acute myelomonocytic leukemia (M4)  
adult acute monoblastic leukemia (M5a)  
recurrent grade 1 follicular lymphoma  
recurrent grade 2 follicular lymphoma  
recurrent grade 3 follicular lymphoma  
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
adult acute monocytic leukemia (M5b)
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

Study placed in the following topic categories:
Thoracic Neoplasms
Prostatic Diseases
Lymphoma, small cleaved-cell, diffuse
Urogenital Neoplasms
Preleukemia
Hemorrhagic Disorders
Multiple myeloma
Lung Neoplasms
Azacitidine
Leukemia, Promyelocytic, Acute
Neoplasm Metastasis
Acute myeloid leukemia, adult
Myelodysplastic syndromes
Lymphoma, Large B-Cell, Diffuse
Non-small cell lung cancer
Immunoproliferative Disorders
4-phenylbutyric acid
Hematologic Diseases
Leukemia, B-cell, chronic
Blood Coagulation Disorders
Acute promyelocytic leukemia
Acute myelogenous leukemia
Leukemia, Myeloid
Genital Diseases, Male
Carcinoma
Multiple Myeloma
B-cell lymphomas
Lung Diseases
Lymphoma, Non-Hodgkin
Acute monoblastic leukemia

Additional relevant MeSH terms:
Antimetabolites
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Disease
Antimetabolites, Antineoplastic
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Pathologic Processes
Therapeutic Uses
Syndrome
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 03, 2008




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