LeukemiaPhase 1/2NCT00075010
Phase I/II Study of Decitabine and Valproic Acid in Relapsed/Refractory Leukemia or Myelodysplastic Syndromes
A Phase 1/2 study testing Decitabine and Valproic acid in people with Leukemia and Myelodysplastic Syndromes, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Valproic acid is a medication that is currently used in the prevention of seizures, bipolar disorder, and migraine headaches. Researchers hope that it may improve the effects of decitabine. Decitabine is a chemotherapy drug with known activity in leukemia and myelodysplastic syndromes. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes
- What is being tested?
- Decitabine and Valproic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jan 2004to 8 Nov 2006
- Phase
- Phase 1/2
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- FOR PHASE I COMPONENT OF THE STUDY: Patients with refractory or relapsed: acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndrome (MDS) are eligible. Patients with chronic lymphocytic leukemia (CLL) are eligible if fludarabine based therapy has failed. Patients with chronic myeloid leukemia (CML) are eligible if they have documented hematologic resistance to imatinib mesylate or have not achieved or lost any cytogenetic response to imatinib mesylate after 12 months of therapy.
- Untreated patients older than 60 years of age with AML or MDS who refuse or are not eligible for frontline chemotherapy, are eligible.
- Performance status of =/< 2 by the ECOG scale.
- Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of UTMDACC.
- Age > 2 years.
- Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Use of hydroxyurea for patients with rapidly proliferative disease is allowed for the first two weeks on therapy. Imatinib mesylate (Gleevec) and anagrelide must also be stopped 2 weeks prior to entering this study.
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- Adequate liver function (bilirubin of < 2mg%, SGPT < 3 x ULN) and renal function (creatinine < 2mg%).
- Women of childbearing potential must practice contraception. Men and women must continue birth control for the duration of the trial.
- INCLUSION OF PHASE II PORTION OF THE STUDY: As in the phase I portion but only patients with AML or high-risk MDS (blasts > or = 10%), including untreated patients older than 60 years of age with AML or MDS who refuse or are not eligible for frontline chemotherapy, will be eligible in this portion of the study.
Who cannot join
- Nursing and pregnant females are excluded.
- Patients with active and uncontrolled infections are excluded.
- Patients with a known ornithine transcarbamylase disorder, history of unexplained coma or a family history of ornithine transcarbamylase disorder are excluded from this study.
- Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, pancreatitis, psychiatric illness that would limit compliance with study requirements.
- Patients with history of hepatitis B, C, alcoholic liver disease or evidence of hepatopathy will be excluded.
- Patients already receiving valproic acid or receiving other anticonvulsivants will be excluded.
- Untreated patients younger than 60 years will not be candidates for this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Study of 5-aza-2'-Deoxycytidine and Valproic Acid in Patients With Relapsed/Refractory Leukemia or Myelodysplastic Syndromes
Valproic acid is a medication that is currently used in the prevention of seizures, bipolar disorder, and migraine headaches. Researchers hope that it may improve the effects of decitabine. Decitabine is a chemotherapy drug with known activity in leukemia and myelodysplastic syndromes.
Read the detailed description
Recent studies have shown synergy between demethylating agents and histone deacetylase inhibitors. It has been shown that both DNA methylation and histone deacetylation work together in affecting gene expression.
Therefore, drugs that inhibit DNA methylation and those that inhibit histone deacetylase can reactivate silenced genes in combination better than they can individually. Decitabine (5 aza-2'deoxycytidine), a drug that produces marked DNA hypomethylator, has demonstrated antileukemic activity at low doses. There are several drugs that have been shown to have histone acetylase activity. One of these is valproic acid that has been used safely for many years as an anti-seizure medication.
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Being tested
- Decitabine, Valproic acid
- Keywords
- Relapsed/Refractory Leukemia, Myelodysplastic Syndromes
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called Dacogen®
15 mg/m^2 by vein over 1 hour times 10 days
Valproic acidDrug
20 mg/kg given orally daily for 10 days
| Study group | Role | What they receive |
|---|---|---|
| Decitabine + Valproic acid | Experimental | Decitabine 15 mg/m^2 by vein over 1 hour times 10 days Receives: Drug: Decitabine; Drug: Valproic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Valproic Acid + Decitabine
MTD is the dose level at which less than two participants develop a dose limiting toxicity (DLT). Response evaluated after completing first cycle, 4-8 weeks of therapy.
Measured: Up to 8 weeks of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2003 (estimated)
- Study start23 Jan 2004
- Primary completion8 Nov 2006
- Study completion8 Nov 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Inc.
- Responsible party
- Sponsor
- Investigators
- Guillermo Garcia-Manero, M.D., Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00075010
- Sponsor's protocol ID
- 2003-0314
- Status last verified
- Nov 2018
- First submitted
- 29 Dec 2003
- Last updated
- 15 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, Yang H, Rosner G, Verstovsek S, Rytting M, Wierda WG, Ravandi F, Koller C, Xiao L, Faderl S, Estrov Z, Cortes J, O'brien S, Estey E, Bueso-Ramos C, Fiorentino J, Jabbour E, Issa JP. Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia. Blood. 2006 Nov 15;108(10):3271-9. doi: 10.1182/blood-2006-03-009142. Epub 2006 Aug 1.
PubMed 16882711
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of 5-aza-2'-Deoxycytidine and Valproic Acid in Patients With Relapsed/Refractory Leukemia or Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT00075010
- Acronym / sponsor ID
- 2003-0314
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Keywords
- Relapsed/Refractory Leukemia, Myelodysplastic Syndromes
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Eisai Inc.
- Study start
- 23 Jan 2004 (actual)
- Primary completion
- 8 Nov 2006 (actual)
- Study completion
- 8 Nov 2006 (actual)
- First posted
- 31 Dec 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.
Valproic acid is a medication that is currently used in the prevention of seizures, bipolar disorder, and migraine headaches. Researchers hope that it may improve the effects of decitabine. Decitabine is a chemotherapy drug with known activity in leukemia and myelodysplastic syndromes.
Detailed description
Recent studies have shown synergy between demethylating agents and histone deacetylase inhibitors. It has been shown that both DNA methylation and histone deacetylation work together in affecting gene expression.
Therefore, drugs that inhibit DNA methylation and those that inhibit histone deacetylase can reactivate silenced genes in combination better than they can individually. Decitabine (5 aza-2'deoxycytidine), a drug that produces marked DNA hypomethylator, has demonstrated antileukemic activity at low doses. There are several drugs that have been shown to have histone acetylase activity. One of these is valproic acid that has been used safely for many years as an anti-seizure medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Decitabine + Valproic acid | Experimental | Drug: Decitabine, Drug: Valproic acidDecitabine 15 mg/m^2 by vein over 1 hour times 10 days |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- FOR PHASE I COMPONENT OF THE STUDY: Patients with refractory or relapsed: acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndrome (MDS) are eligible. Patients with chronic lymphocytic leukemia (CLL) are eligible if fludarabine based therapy has failed. Patients with chronic myeloid leukemia (CML) are eligible if they have documented hematologic resistance to imatinib mesylate or have not achieved or lost any cytogenetic response to imatinib mesylate after 12 months of therapy.
- Untreated patients older than 60 years of age with AML or MDS who refuse or are not eligible for frontline chemotherapy, are eligible.
- Performance status of =/< 2 by the ECOG scale.
- Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of UTMDACC.
- Age > 2 years.
Key exclusion criteria (7 listed)
- Nursing and pregnant females are excluded.
- Patients with active and uncontrolled infections are excluded.
- Patients with a known ornithine transcarbamylase disorder, history of unexplained coma or a family history of ornithine transcarbamylase disorder are excluded from this study.
- Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, pancreatitis, psychiatric illness that would limit compliance with study requirements.
- Patients with history of hepatitis B, C, alcoholic liver disease or evidence of hepatopathy will be excluded.
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 |
|---|---|---|
| DecitabineAlso: Dacogen®15 mg/m^2 by vein over 1 hour times 10 days | Drug | Decitabine + Valproic acid |
| Valproic acid20 mg/kg given orally daily for 10 days | Drug | Decitabine + Valproic acid |
Primary outcome
Maximum Tolerated Dose (MTD) of Valproic Acid + Decitabine
Time frame: Up to 8 weeks of therapy
MTD is the dose level at which less than two participants develop a dose limiting toxicity (DLT). Response evaluated after completing first cycle, 4-8 weeks of therapy.
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 15 Nov 2018.
- Derived from this study: PubMed 16882711Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, Yang H, Rosner G, Verstovsek S, Rytting M, Wierda WG, Ravandi F, Koller C, Xiao L, Faderl S, Estrov Z, Cortes J, O'brien S, Estey E, Bueso-Ramos C, Fiorentino J, Jabbour E, Issa JP. Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia. Blood. 2006 Nov 15;108(10):3271-9. doi: 10.1182/blood-2006-03-009142. Epub 2006 Aug 1.
- M.D. Anderson Cancer Center's websiteLink provided by the sponsor.
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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.
Guillermo Garcia-Manero, M.D. principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Decitabine and Valproic acid in people with Leukemia and Myelodysplastic Syndromes, run by M.D. Anderson Cancer Center 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?
The sponsor lists 9 inclusion and 7 exclusion criteria. 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 15 Nov 2018. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of Valproic Acid + Decitabine (time frame: Up to 8 weeks of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00075010, which also lists 1 linked publication.
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 15 Nov 2018.