Myelodysplastic SyndromePhase 2NCT00414310
Decitabine (DAC) w/ or w/o Valproic Acid (VPA) in Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)
A Phase 2 study testing Decitabine and Valproic Acid in people with Myelodysplastic Syndrome and Acute Myelogenous Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find out if decitabine, given with or without valproic acid, can help to control AML or MDS. The safety of both treatments will also be studied. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Myelodysplastic Syndrome, Acute Myelogenous Leukemia
- What is being tested?
- Decitabine and Valproic Acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to May 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with MDS and > 5% blasts or IPSS risk intermediate or high; patients with CMML; patients with AML who are age 60 or older. No prior intensive chemotherapy or high-dose ara-C (> 1g/m2). No prior azacytidine for 3 cycles or more or prior decitabine for 2 cycles or more. Prior biologic therapies, targeted therapies, or single agent chemotherapy allowed.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.
- Continued from #1: Hydroxyurea is permitted for control of counts prior to treatment. Procrit, granulocyte colony-stimulating factor (GCSF) are allowed before therapy. Procrit, GCSF or other growth factors are permitted on therapy. Use of hydroxyurea with rapidly proliferative disease is allowed for the first two weeks on therapy.
- Performance 0-2 (ECOG). Adequate liver function (bilirubin of < 2mg/dl) and renal function (creatinine < 2mg/dl). Adequate cardiac functions (NYHA cardiac III-IV excluded). ALT < 2.5x institutional upper limit of normal.
- Signed informed consent.
Who cannot join
- Nursing and pregnant females. Patients of childbearing potential should practice effective methods of contraception. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Active and uncontrolled infections.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
- Known ornithine transcarbamylase disorder.
- Patients requiring continuous valproic acid treatment for the control of seizure disorders.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase II Randomized Study of Low-Dose Decitabine (5-AZA-2'-Deoxycytidine) With or Without Valproic Acid in Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia -"SPORE"
The goal of this clinical research study is to find out if decitabine, given with or without valproic acid, can help to control AML or MDS. The safety of both treatments will also be studied.
Read the detailed description
Decitabine and valproic acid are both designed to cause changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may cause cancer cells to die. Researchers want to see if a combination of valproic acid with decitabine can help improve disease response as well as how long responses last in treating MDS and AML.
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups. Participants in one group will receive decitabine. Participants in the other group will receive decitabine and valproic acid. You will have an equal chance of being assigned to either group at first. After 20 participants are enrolled in each group, you will have a greater chance of being assigned to the group that is showing better results.
Participants in both groups will receive decitabine on Day 1 through a central venous catheter (CVC) in a vein over 1 hour each day for 5 days. A central venous catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure. Participants who are assigned to also get valproic acid will take the drug by mouth on Days 1-7 (7 days in a row).
On Day 0 (the day before treatment begins) or on Day 1, you will have a physical exam, including measurement of your vital signs. Blood (about 2 teaspoons) will be drawn on or about Days 0 or 1, 5, and 10 (if your routine blood tests were found to be abnormal) to learn the status of the disease.
Routine blood draws (about 4 teaspoons) will be done 1-2 times weekly for the first cycle and then every 2-4 weeks in further cycles. You will have another bone marrow aspiration to check disease response to treatment, and then you will have one every 1-3 cycles. One (1) cycle of treatment is 4-8 weeks long.
You may remain on this study as long as you are benefitting or up to 2 years after you first achieve a complete response. Your dose level may be decreased depending on the side effects you may experience. However, if the disease gets worse or you experience any intolerable side effects, you will be taken off this study.
This is an investigational study. Decitabine is FDA approved and commercially available for the treatment of MDS. Valproic acid is FDA approved and commercially available for the treatment of seizure disorders. Up to 150 patients will take part in this study. All will be enrolled at MD Anderson.
- Being tested
- Decitabine, Valproic Acid
- Keywords
- Decitabine, Dacogen, 5-AZA, Valproic Acid, Myelodysplastic Syndrome, Acute Myelogenous Leukemia, MDS, AML
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called Dacogen
20 mg/m^2 IV over 1 hour daily for 5 days.
Valproic AcidDrug
50 mg/kg orally daily for 7 days
| Study group | Role | What they receive |
|---|---|---|
| Decitabine | Experimental | Decitabine 20 mg/m^2 intravenous (IV) over 1 hour daily for 5 days. Receives: Drug: Decitabine |
| Decitabine + Valproic Acid | Experimental | Decitabine 20 mg/m^2 intravenous (IV) over 1 hour daily for 5 days. Valproic Acid 50 mg/kg orally daily for 7 days. Receives: Drug: Decitabine; Drug: Valproic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participant Response Rates to Decitabine With or Without Valproic Acid in MDS and AML
Complete Remission (CR): CR defined as normalization of peripheral blood and bone marrow with < 5% bone marrow blasts, a peripheral blood granulocyte count > (1.0 x 10^9/ L, and a platelet count > 100 x 10^9/L). CRi or complete remission with incomplete platelet recovery is defined as above, but platelets <100 x 109/L. Partial Remission: as above except for the presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment. Clinical Benefit: In MDS/CMML, as per International Working Group (IWG) criteria, platelets increase by 50% and to above 30 x 10^9/L untransfused (if lower than that pretherapy); or granulocytes increase by 100% and to above 10^9/L (if lower than that pretherapy); or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by > 50%; or monocytosis reduction by > 50% if pretreatment > 5 x 10^9/L. In addition to IWG criteria, in AML, a decrease in bone marrow blasts to <5% also considered clinical benefit.
Measured: 1 Year
Secondary outcomes (2)
Response Duration
The date of Response to the date of loss of response or last follow-up.
Measured: Up to 60 months
Overall Survival Rate
Time from date of treatment start until date of death due to any cause or last Follow-up.
Measured: Up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2006 (estimated)
- Study startDec 2006
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic SyndromeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 153 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
- Hagop Kantarjian, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00414310
- Sponsor's protocol ID
- 2006-0686
- Other IDs
- NCI-2012-01396
- Status last verified
- May 2019
- First submitted
- 19 Dec 2006
- Last updated
- 21 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Study of Low-Dose Decitabine (5-AZA-2'-Deoxycytidine) With or Without Valproic Acid in Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia -"SPORE"
- ClinicalTrials.gov ID
- NCT00414310
- Acronym / sponsor ID
- 2006-0686
- Keywords
- Decitabine, Dacogen, 5-AZA, Valproic Acid, Myelodysplastic Syndrome, Acute Myelogenous Leukemia, MDS, AML
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Eisai Inc.
- Study start
- Dec 2006
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 21 Dec 2006 (estimated)
- Results
- Posted 13 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to find out if decitabine, given with or without valproic acid, can help to control AML or MDS. The safety of both treatments will also be studied.
Detailed description
Decitabine and valproic acid are both designed to cause changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may cause cancer cells to die. Researchers want to see if a combination of valproic acid with decitabine can help improve disease response as well as how long responses last in treating MDS and AML.
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups. Participants in one group will receive decitabine. Participants in the other group will receive decitabine and valproic acid. You will have an equal chance of being assigned to either group at first. After 20 participants are enrolled in each group, you will have a greater chance of being assigned to the group that is showing better results.
Participants in both groups will receive decitabine on Day 1 through a central venous catheter (CVC) in a vein over 1 hour each day for 5 days. A central venous catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure. Participants who are assigned to also get valproic acid will take the drug by mouth on Days 1-7 (7 days in a row).
On Day 0 (the day before treatment begins) or on Day 1, you will have a physical exam, including measurement of your vital signs. Blood (about 2 teaspoons) will be drawn on or about Days 0 or 1, 5, and 10 (if your routine blood tests were found to be abnormal) to learn the status of the disease.
Routine blood draws (about 4 teaspoons) will be done 1-2 times weekly for the first cycle and then every 2-4 weeks in further cycles. You will have another bone marrow aspiration to check disease response to treatment, and then you will have one every 1-3 cycles. One (1) cycle of treatment is 4-8 weeks long.
You may remain on this study as long as you are benefitting or up to 2 years after you first achieve a complete response. Your dose level may be decreased depending on the side effects you may experience. However, if the disease gets worse or you experience any intolerable side effects, you will be taken off this study.
This is an investigational study. Decitabine is FDA approved and commercially available for the treatment of MDS. Valproic acid is FDA approved and commercially available for the treatment of seizure disorders. Up to 150 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Decitabine | Experimental | Drug: DecitabineDecitabine 20 mg/m^2 intravenous (IV) over 1 hour daily for 5 days. |
| Decitabine + Valproic Acid | Experimental | Drug: Decitabine, Drug: Valproic AcidDecitabine 20 mg/m^2 intravenous (IV) over 1 hour daily for 5 days. Valproic Acid 50 mg/kg orally daily for 7 days. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with MDS and > 5% blasts or IPSS risk intermediate or high; patients with CMML; patients with AML who are age 60 or older. No prior intensive chemotherapy or high-dose ara-C (> 1g/m2). No prior azacytidine for 3 cycles or more or prior decitabine for 2 cycles or more. Prior biologic therapies, targeted therapies, or single agent chemotherapy allowed.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.
- Continued from #1: Hydroxyurea is permitted for control of counts prior to treatment. Procrit, granulocyte colony-stimulating factor (GCSF) are allowed before therapy. Procrit, GCSF or other growth factors are permitted on therapy. Use of hydroxyurea with rapidly proliferative disease is allowed for the first two weeks on therapy.
- Performance 0-2 (ECOG). Adequate liver function (bilirubin of < 2mg/dl) and renal function (creatinine < 2mg/dl). Adequate cardiac functions (NYHA cardiac III-IV excluded). ALT < 2.5x institutional upper limit of normal.
- Signed informed consent.
Key exclusion criteria (5 listed)
- Nursing and pregnant females. Patients of childbearing potential should practice effective methods of contraception. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Active and uncontrolled infections.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
- Known ornithine transcarbamylase disorder.
- Patients requiring continuous valproic acid treatment for the control of seizure disorders.
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: Dacogen20 mg/m^2 IV over 1 hour daily for 5 days. | Drug | Decitabine, Decitabine + Valproic Acid |
| Valproic Acid50 mg/kg orally daily for 7 days | Drug | Decitabine + Valproic Acid |
Primary outcome
Participant Response Rates to Decitabine With or Without Valproic Acid in MDS and AML
Time frame: 1 Year
Complete Remission (CR): CR defined as normalization of peripheral blood and bone marrow with < 5% bone marrow blasts, a peripheral blood granulocyte count > (1.0 x 10^9/ L, and a platelet count > 100 x 10^9/L). CRi or complete remission with incomplete platelet recovery is defined as above, but platelets <100 x 109/L. Partial Remission: as above except for the presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment. Clinical Benefit: In MDS/CMML, as per International Working Group (IWG) criteria, platelets increase by 50% and to above 30 x 10^9/L untransfused (if lower than that pretherapy); or granulocytes increase by 100% and to above 10^9/L (if lower than that pretherapy); or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by > 50%; or monocytosis reduction by > 50% if pretreatment > 5 x 10^9/L. In addition to IWG criteria, in AML, a decrease in bone marrow blasts to <5% also considered clinical benefit.
2 secondary outcomes
Response Duration
Time frame: Up to 60 months
Overall Survival Rate
Time frame: Up to 7 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center 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.
Hagop Kantarjian, MD 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 2 study testing Decitabine and Valproic Acid in people with Myelodysplastic Syndrome and Acute Myelogenous Leukemia, 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 4 inclusion and 5 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 21 May 2019. 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 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?
Yes. Results are posted in the registry (first posted 13 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Participant Response Rates to Decitabine With or Without Valproic Acid in MDS and AML (time frame: 1 Year). It is what the study was designed to measure, not a finding.
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 21 May 2019.