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Decitabine (DAC) w/ or w/o Valproic Acid (VPA) in Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)

This study has been completed.
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00414310
First received: December 19, 2006
Last updated: July 15, 2015
Last verified: July 2015

December 19, 2006
July 15, 2015
December 2006
May 2015   (final data collection date for primary outcome measure)
Participant Response Rates to Decitabine With or Without Valproic Acid in MDS and AML [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
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.
Primary: Compare the response rates to decitabine with or without valproic acid in MDS and AML.
Complete list of historical versions of study NCT00414310 on ClinicalTrials.gov Archive Site
Participant Response Durations/Length of Survival [ Time Frame: 1 Year or to disease progression ] [ Designated as safety issue: No ]
The following scoring system used for patient outcomes: For a patient who died, his/her score is the actual number of weeks he/she survived since the beginning of treatment. For a patient who is still alive, his/her score is the number of weeks he/she has survived since the beginning of treatment plus a number which depends on his/her current status. Based on the median survival weeks in historical data, these numbers will be 40 for those patients who go off-study (resistant), 60 for patients without response but on study, 75 for patients with CRi or PR, and 110 for patients who have achieved CR.
Secondary: Compare response durations, survivals and side effects of the two regimens. Compare epigenetic modulation (gene expression, hypomethylation, histone acetylation) between the two regimens.
Not Provided
Not Provided
 
Decitabine (DAC) w/ or w/o Valproic Acid (VPA) in Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Myelodysplastic Syndrome
  • Acute Myelogenous Leukemia
  • Drug: Decitabine
    20 mg/m^2 IV over 1 hour daily for 5 days.
    Other Name: Dacogen
  • Drug: Valproic Acid
    50 mg/kg orally daily for 7 days
  • Experimental: Decitabine
    Decitabine 20 mg/m^2 intravenous (IV) over 1 hour daily for 5 days.
    Intervention: Drug: Decitabine
  • Experimental: Decitabine + Valproic Acid
    Decitabine 20 mg/m^2 intravenous (IV) over 1 hour daily for 5 days. Valproic Acid 50 mg/kg orally daily for 7 days.
    Interventions:
    • Drug: Decitabine
    • Drug: Valproic Acid
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
153
May 2015
May 2015   (final data collection date for primary outcome measure)

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, 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.
  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.
Both
Child, Adult, Senior
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00414310
2006-0686, NCI-2012-01396
Yes
Not Provided
Not Provided
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Eisai Inc.
Principal Investigator: Hagop Kantarjian, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP