LeukemiaPhase 1NCT00004871
Azacitidine Plus Phenylbutyrate in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
A Phase 1 study testing azacitidine and sodium phenylbutyrate in people with Leukemia and Myelodysplastic Syndromes, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- What is being tested?
- azacitidine and sodium phenylbutyrate
- How many people
- Not given
- Where
- 1 siteUnited States
- Study dates
- May 2000to not given
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed myelodysplastic syndrome (MDS) indicating one of the following:
- Refractory anemia (RA)
- Primary refractory leukopenia or thrombocytopenia with MDS morphology
- RA with excess blasts (RAEB)
- RA with ringed sideroblasts (RARS)
- Chronic myelomonocytic leukemia
- RAEB in transformation
- RA or RARS must have at least one of the following:
- Absolute neutrophil count less than 1,000/mm^3
- Untransfused hemoglobin less than 8 g/dL
- Platelet count less than 20,000/mm^3
- Anemia
- Thrombocytopenia requiring transfusion
- High risk chromosomal abnormalities
- Any stage of MDS allowed including:
- Previously untreated MDS
- Refractory MDS allowed if failure to achieve remission following prior intensive chemotherapy of at least 1 month ago
- Relapsed, refractory, or untreated acute myeloid leukemia (AML) with the following:
- WBC less than 30,000/mm^3
- Stable for at least 2 weeks
- Unlikely to require cytotoxic therapy during study
- Untreated AML with poor risk factors for response to standard therapy including:
- Greater than 60 years old
- AML occurs in setting of antecedent hematologic disorder
- High risk chromosomes (e.g., abnormalities of chromosome 5 or 7 or complex cytogenetic abnormalities)
- Medical conditions that preclude cytotoxic chemotherapy as primary therapy
- Refusal of cytotoxic chemotherapy allowed
- No clinical evidence of CNS leukostasis or CNS leukemia
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Zubrod 0-2
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
- Hemoglobin at least 8 g/dL (transfusion allowed)
Hepatic:
- Bilirubin less than 2.0 mg/dL (unless due to hemolysis or Gilbert's disease)
Renal:
- Creatinine less than 2.0 mg/dL
Cardiovascular:
- No disseminated intravascular coagulation
Pulmonary:
- No pulmonary leukostasis
Other:
- No active infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception 2 weeks prior, during and 3 months after study
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 3 weeks since prior biologic therapy including colony stimulating factors and recovered
Chemotherapy:
- See Disease Characteristics
- At least 3 weeks since prior chemotherapy and recovered
Endocrine therapy:
- At least 3 weeks since prior hormonal therapy and recovered
Radiotherapy:
- At least 3 weeks since prior radiotherapy and recovered
Surgery:
- Not specified
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
About this study
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)
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.
Read the detailed description
OBJECTIVES:
- Determine the safety and toxicity of azacitidine in combination with phenylbutyrate in patients with recurrent, refractory, or untreated acute myeloid leukemia or myelodysplastic syndrome.
- Determine the minimal effective pharmacologic dose of azacitidine required to consistently inhibit DNA methyltransferase in this patient population.
- Obtain preliminary clinical and/or laboratory data suggesting potential therapeutic activity of this combination regimen in these patients.
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.
- Being tested
- azacitidine, sodium phenylbutyrate
- Keywords
- 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
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Leukemia, Myeloid, Acute, Anemia, Refractory, Anemia, Refractory, with Excess of Blasts, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
azacitidineDrug
sodium phenylbutyrateDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startMay 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Steven D. Gore, MD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00004871
- Sponsor's protocol ID
- CDR0000067531, J9950
- Other IDs
- U01CA070095, R01CA067803, P30CA006973, JHOC-99072307, NCI-T99-0092, JHOC-J9950
- Status last verified
- Mar 2010
- First submitted
- 7 Mar 2000
- Last updated
- 10 Mar 2010
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00004871
- Acronym / sponsor ID
- CDR0000067531, J9950
- Keywords
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2000
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
- Determine the safety and toxicity of azacitidine in combination with phenylbutyrate in patients with recurrent, refractory, or untreated acute myeloid leukemia or myelodysplastic syndrome.
- Determine the minimal effective pharmacologic dose of azacitidine required to consistently inhibit DNA methyltransferase in this patient population.
- Obtain preliminary clinical and/or laboratory data suggesting potential therapeutic activity of this combination regimen in these patients.
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| azacitidine | Drug | – |
| sodium phenylbutyrate | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven D. Gore, MD study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing azacitidine and sodium phenylbutyrate in people with Leukemia and Myelodysplastic Syndromes, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2010.