LeukemiaPhase 1NCT00006239
Phenylbutyrate and Tretinoin in Treating Patients With Hematologic Cancer
A Phase 1 study testing sodium phenylbutyrate and tretinoin 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: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Tretinoin may help hematologic cancer cells develop into normal white blood cells. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- What is being tested?
- sodium phenylbutyrate and tretinoin
- How many people
- Not given
- Where
- 1 siteUnited States
- Study dates
- Dec 2000to Mar 2005
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed myelodysplastic syndrome (MDS)
- Refractory anemia
- Primary refractory leukopenia or thrombocytopenia with morphologic features of MDS
- Refractory anemia with excess blasts (RAEB)
- Refractory anemia with ringed sideroblasts
- RAEB in transformation
- Must have excess blasts or be hematopoietically compromised, defined as one of the following:
- RBC transfusion dependent
- Granulocyte count less than 1,000/mm^3
- Platelet count less than 50,000/mm^3 OR
- Diagnosis of chronic myelomonocytic leukemia
- Hematopoietically compromised (as defined above) OR
- Excess blasts OR
- Evaluable disease related symptomatology (organomegaly or leukemia cutis) OR
- Diagnosis of acute myeloid leukemia
- WBC less than 20,000/mm^3 and stable for at least 2 weeks
- Unlikely to require cytotoxic therapy during study
- No CNS or pulmonary 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)
- No disseminated intravascular coagulation
Hepatic:
- Bilirubin less than 2.0 mg/dL (unless due to hemolysis or Gilbert's syndrome)
Renal:
- Creatinine less than 2.0 mg/dL
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception for 2 weeks prior, during, and for 3 months after study
- No active infection
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
- At least 3 weeks since prior biologic therapy, including hematopoietic growth factors, and recovered
Chemotherapy:
- See Disease Characteristics
- At least 3 weeks (1 month for MDS patients) since prior chemotherapy and recovered
Endocrine therapy:
- Not specified
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: A Phase I, Dose-Finding Trial of Sodium Phenylbutrate (NSC 657802) in Combination With All Trans-retinoic Acid (ATRA, NSC 122758) in Patients With Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Tretinoin may help hematologic cancer cells develop into normal white blood cells.
PURPOSE: Phase I trial to study the effectiveness of combining phenylbutyrate and tretinoin in treating patients who have hematologic cancer.
Read the detailed description
OBJECTIVES:
- Determine the safety and toxicity of phenylbutyrate and tretinoin in patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.
- Determine the pharmacokinetic interaction of this regimen in these patients.
- Determine any potential therapeutic activity of this regimen in these patients.
OUTLINE: This is a dose escalation study of tretinoin.
Patients receive phenylbutyrate IV continuously on days 1-7 of weeks 1, 5, 7, 9, 11, 13, 15, 17, and 19. Patients also receive oral tretinoin three times daily on days 1-7 of weeks 3, 5, 7, 9, 11, 13, 15, 17, and 19. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tretinoin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose limiting toxicities.
An additional cohort of 6 patients is accrued at the MTD. These patients receive phenylbutyrate IV continuously on days 1-3 of weeks 1 and 3-18. These patients also receive oral tretinoin three times daily on days 1-3 of weeks 2-18. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 18 months.
- Being tested
- sodium phenylbutyrate, tretinoin
- 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, previously treated myelodysplastic syndromes, atypical chronic myeloid leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12)
- 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.
sodium phenylbutyrateDrug
tretinoinDrug
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 startDec 2000
- Primary completionFeb 2005
- Study completionMar 2005
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)
- Responsible party
- Sponsor
- Investigators
- Steven D. Gore, MD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006239
- Sponsor's protocol ID
- J9879 CDR0000068164
- Other IDs
- R01CA067803, P30CA006973, JHOC-J9879, JHOC-99072306, NCI-T98-0068
- Status last verified
- Sep 2017
- First submitted
- 11 Sep 2000
- Last updated
- 29 Sep 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Dose-Finding Trial of Sodium Phenylbutrate (NSC 657802) in Combination With All Trans-retinoic Acid (ATRA, NSC 122758) in Patients With Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT00006239
- Acronym / sponsor ID
- J9879 CDR0000068164
- 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, previously treated 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
- Dec 2000
- Primary completion
- Feb 2005 (actual)
- Study completion
- Mar 2005 (actual)
- 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: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Tretinoin may help hematologic cancer cells develop into normal white blood cells.
PURPOSE: Phase I trial to study the effectiveness of combining phenylbutyrate and tretinoin in treating patients who have hematologic cancer.
Detailed description
OBJECTIVES:
- Determine the safety and toxicity of phenylbutyrate and tretinoin in patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.
- Determine the pharmacokinetic interaction of this regimen in these patients.
- Determine any potential therapeutic activity of this regimen in these patients.
OUTLINE: This is a dose escalation study of tretinoin.
Patients receive phenylbutyrate IV continuously on days 1-7 of weeks 1, 5, 7, 9, 11, 13, 15, 17, and 19. Patients also receive oral tretinoin three times daily on days 1-7 of weeks 3, 5, 7, 9, 11, 13, 15, 17, and 19. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tretinoin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose limiting toxicities.
An additional cohort of 6 patients is accrued at the MTD. These patients receive phenylbutyrate IV continuously on days 1-3 of weeks 1 and 3-18. These patients also receive oral tretinoin three times daily on days 1-3 of weeks 2-18. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 18 months.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 120 years
- 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 |
|---|---|---|
| sodium phenylbutyrate | Drug | – |
| tretinoin | 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 29 Sep 2017.
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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 sodium phenylbutyrate and tretinoin 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 29 Sep 2017. 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 29 Sep 2017.