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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00414310
Recruitment Status : Completed
First Posted : December 21, 2006
Results First Posted : August 13, 2015
Last Update Posted : August 13, 2015
Eisai Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome Acute Myelogenous Leukemia Drug: Decitabine Drug: Valproic Acid Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 153 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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"
Study Start Date : December 2006
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Arm Intervention/treatment
Experimental: Decitabine
Decitabine 20 mg/m^2 intravenous (IV) over 1 hour daily for 5 days.
Drug: Decitabine
20 mg/m^2 IV over 1 hour daily for 5 days.
Other Name: Dacogen

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.
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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Participant Response Durations/Length of Survival [ Time Frame: 1 Year or to disease progression ]
    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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00414310

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Eisai Inc.
Principal Investigator: Hagop Kantarjian, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00414310     History of Changes
Other Study ID Numbers: 2006-0686
NCI-2012-01396 ( Registry Identifier: NCI CTRP )
First Posted: December 21, 2006    Key Record Dates
Results First Posted: August 13, 2015
Last Update Posted: August 13, 2015
Last Verified: July 2015

Keywords provided by M.D. Anderson Cancer Center:
Valproic Acid
Myelodysplastic Syndrome
Acute Myelogenous Leukemia

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Valproic Acid
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs