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| Sponsor: | Sidney Kimmel Comprehensive Cancer Center |
|---|---|
| Collaborator: |
National Cancer Institute (NCI) |
| Information provided by: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00004871 |
Purpose
RATIONALE: Azacitidine plus phenylbutyrate may help leukemia cells develop into normal white blood cells.
PURPOSE: Phase I trial to study the effectiveness of combining azacitidine and phenylbutyrate in treating patients who have acute myeloid leukemia or myelodysplastic syndrome.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases |
Drug: azacitidine Drug: sodium phenylbutyrate |
Phase I |
| Study Type: | Interventional |
| Study Design: | Treatment |
| Official Title: | Phase I, Dose De-Escalation to Minimal Effective Pharmacologic Dose Trial of Sodium Phenylbutyrate (PB, NSC 657802) in Combination With 5-Azacytidine (5-AZA, NSC 102816) in Patients With Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) |
| Study Start Date: | May 2000 |
OBJECTIVES:
OUTLINE: This is a dose deescalation study of azacitidine.
Patients receive azacitidine subcutaneously daily on days 1-5 and 29-33 followed by phenylbutyrate IV continuously on days 5-12 and 33-40. Treatment continues for at least 2 courses in the absence of disease progression. Patients with responsive disease may receive an additional 2 months of therapy.
Cohorts of 3-6 patients receive deescalating doses of azacitidine until the minimal effective pharmacologic dose (MEPD) is determined. The MEPD is defined as the dose above the dose at which more than 1 of 6 patients do not meet the target enzyme inhibition of greater than 90%.
Once the MEPD and toxicity have been established for a 5 day schedule, daily dose schedule of azacitidine is increased to 10, 14, and 21 days, followed by phenylbutyrate for 7 days. Courses are repeated every 28 days.
PROJECTED ACCRUAL: Approximately 32 patients will be accrued for this study within 2 years.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed myelodysplastic syndrome (MDS) indicating one of the following:
RA or RARS must have at least one of the following:
Any stage of MDS allowed including:
Relapsed, refractory, or untreated acute myeloid leukemia (AML) with the following:
Untreated AML with poor risk factors for response to standard therapy including:
PATIENT CHARACTERISTICS:
Age:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Pulmonary:
Other:
PRIOR CONCURRENT THERAPY:
Biologic therapy:
Chemotherapy:
Endocrine therapy:
Radiotherapy:
Surgery:
Contacts and Locations| United States, Maryland | |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | |
| Baltimore, Maryland, United States, 21231-2410 | |
| Study Chair: | Steven D. Gore, MD | Sidney Kimmel Comprehensive Cancer Center |
More Information
| Study ID Numbers: | CDR0000067531, JHOC-99072307, NCI-T99-0092, JHOC-J9950 |
| Study First Received: | March 7, 2000 |
| Last Updated: | July 23, 2008 |
| ClinicalTrials.gov Identifier: | NCT00004871 History of Changes |
| Health Authority: | United States: Federal Government |
|
recurrent adult acute myeloid leukemia untreated adult acute myeloid leukemia refractory anemia refractory anemia with ringed sideroblasts refractory anemia with excess blasts refractory anemia with excess blasts in transformation |
chronic myelomonocytic leukemia de novo myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes atypical chronic myeloid leukemia myelodysplastic/myeloproliferative disease, unclassifiable |
|
Antimetabolites Antimetabolites, Antineoplastic Disease Neoplasms by Histologic Type Molecular Mechanisms of Pharmacological Action Precancerous Conditions Antineoplastic Agents 4-phenylbutyric acid Hematologic Diseases Myelodysplastic Syndromes Myeloproliferative Disorders Enzyme Inhibitors |
Leukemia, Myeloid Leukemia, Myeloid, Acute Pharmacologic Actions Leukemia Preleukemia Neoplasms Pathologic Processes Therapeutic Uses Syndrome Azacitidine Myelodysplastic-Myeloproliferative Diseases Bone Marrow Diseases |