Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI MSKCC-99060 NCI-T99-0091, NCT00006019, T99-0091

Objectives

1. 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.
2. 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.
3. Determine the effect of this treatment regimen upon gene methylation and histone acetylation in target cells in these patients.
4. Determine the technical feasibility of serially monitoring transcriptional activity and methylation status of selected genes in vivo in these patients.
5. Determine the safety and potential antitumor efficacy of this treatment regimen in these patients.

Entry 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.]

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

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/mm³
  • Platelet count at least 75,000/mm³

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

Expected Enrollment

A total of 20 patients will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Peter Maslak, MD, Protocol chair		Ph: 212-639-5518; 800-525-2225 Email: maslakp@mskcc.org

Registry Information
Official Title		Pilot Study of Sodium Phenylbutyrate Plus Azacytidine
Trial Start Date		2000-05-09
Registered in ClinicalTrials.gov		NCT00006019
Date Submitted to PDQ		2000-05-30
Information Last Verified		2002-10-01
NCI Grant/Contract Number		P30-CA08748