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"
N/A
N/A
Both
Myelodysplastic Syndrome, Acute Myelogenous Leukemia
Trial Information
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"
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.
Inclusion Criteria:
1. 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.
2. Continued from #1: Hydroxyurea is permitted for control of counts prior to treatment.
Procrit, 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.
3. 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.
4. Signed informed consent.
Exclusion Criteria:
1. 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.
2. Active and uncontrolled infections.
3. 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.
4. Known ornithine transcarbamylase disorder.
5. Patients requiring continuous valproic acid treatment for the control of seizure
disorders.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response rates to decitabine with or without valproic acid in MDS and AML.
Outcome Time Frame:
1 Year
Safety Issue:
No
Principal Investigator
Hagop Kantarjian, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2006-0686
NCT ID:
NCT00414310
Start Date:
December 2006
Completion Date:
December 2014
Related Keywords:
- Myelodysplastic Syndrome
- Acute Myelogenous Leukemia
- Decitabine
- Dacogen
- 5-AZA
- Valproic Acid
- Myelodysplastic Syndrome
- Acute Myelogenous Leukemia
- MDS
- AML
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
