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 - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	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

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

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

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

Drug Information available for: Azacitidine Sodium phenylbutyrate

U.S. FDA Resources

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

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000068030, MSKCC-99060, NCI-T99-0091
Study First Received:	July 5, 2000
Last Updated:	November 16, 2008
ClinicalTrials.gov Identifier:	NCT00006019 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent non-small cell lung cancer
refractory multiple myeloma
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

Additional relevant MeSH terms:

Thoracic Neoplasms
Antimetabolites, Antineoplastic
Prostatic Diseases
Molecular Mechanisms of Pharmacological Action
Urogenital Neoplasms
Preleukemia
Neoplasms by Site
Hemorrhagic Disorders
Pathologic Processes
Lung Neoplasms
Therapeutic Uses
Azacitidine
Cardiovascular Diseases
Immunoproliferative Disorders
Immune System Diseases

Hematologic Diseases
4-phenylbutyric acid
Leukemia, Myeloid
Genital Diseases, Male
Carcinoma
Multiple Myeloma
Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Prostatic Neoplasms
Neoplasms, Glandular and Epithelial
Antimetabolites
Precancerous Conditions
Genital Neoplasms, Male
Blood Protein Disorders

ClinicalTrials.gov processed this record on November 30, 2009