Azacytidine With Valproic Acid Versus Ara-C in Acute Myeloid Leukemia (AML)/ Myelodysplastic Syndrome (MDS) Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00382590
First received: September 27, 2006
Last updated: August 1, 2012
Last verified: August 2012
  Purpose

Primary Objective:

1. To evaluate whether 5 azacytidine (5-aza)/valproic acid (VPA) or low dose ara-C produces longer event free survival time in patients age > or = 60 years with untreated Acute Myeloid Leukemia (AML) or high risk Myelodysplastic Syndrome (MDS) who are typically ineligible for, or not placed on, studies of new agents.

Secondary Objective:

1. To evaluate whether pre-treatment methylation/acetylation status in AML/MDS blasts predicts response to either therapy or whether the ability of the 5 azacytidine + valproic acid combination to induce demethylation or acetylation parallels response.


Condition Intervention Phase
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Leukemia
Drug: 5-Azacytidine
Drug: Ara-C
Drug: Valproic Acid (VPA)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of the Combination of 5-Azacytidine With Valproic Acid (VPA) Versus Low-Dose Ara-C in Patients With AML/MDS Not Eligible for Other Studies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Participants With Response [ Time Frame: Evaluated every 3 weeks, following 4 courses (16/24 weeks ) and till study end ] [ Designated as safety issue: Yes ]
    Patient response defined by: Death, Resistant to Therapy [no major hematologic improvement using International Myelodysplastic Syndromes (MDS) Working Group (Cheson B, Bennett J, Kantarjian H et al, Blood 2006) criteria after a maximum of 4 courses], or Relapse.


Enrollment: 11
Study Start Date: August 2005
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 5-Aza + VPA
5-Azacytidine (5-Aza) 75 mg/m^2 subcutaneously daily + Valproic Acid (VPA) 50 mg/m^2 orally daily, each for 7 days
Drug: 5-Azacytidine
75 mg/m^2 daily for 7 days (days 1-7) via subcutaneous injection.
Other Names:
  • Azacytidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
Drug: Valproic Acid (VPA)
50 mg/m^2 orally daily days 1-7.
Other Names:
  • VPA
  • Depakene
Active Comparator: Ara-C
Low-Dose Ara-C 20 mg twice daily subcutaneously for 10 days.
Drug: Ara-C
20 mg twice daily via subcutaneous injection for 10 days.
Other Names:
  • Cytarabine
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride

Detailed Description:

5-aza is a chemotherapy drug with activity in leukemia and MDS. Researchers hope that VPA will increase the effects of 5-aza. Low-dose Cytarabine (ara-C) is considered the standard of care for the treatment of leukemia and MDS in older patients not eligible for other therapies.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have blood drawn (about 2 teaspoons) for routine tests. You will also have a bone marrow biopsy and aspiration performed. To collect a bone marrow biopsy/aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.

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 one of two treatment groups. Participants in one group will receive 5-aza and VPA. Participants in the other group will receive ara-C alone. At first, there will be an equal chance of being assigned to either group. As the study goes along, however, the chance of being assigned to the treatment that has worked best so far will increase.

Participants in the 5-aza and VPA group will receive 5-aza as an injection under the skin once a day for 7 days in a row. On these same 7 days, participants in this group will also take VPA by mouth twice a day or 3 times a day based on your weight. Seven (7) days is considered 1 treatment cycle. Both drugs will be taken at the same time. Cycles will be repeated every 4 to 6 weeks.

Participants in the ara-C group will receive ara-c twice a day as an injection under the skin for 10 days (1 cycle). Cycles will be repeated every 4 to 6 weeks.

You will be monitored with routine blood tests (about 1-2 teaspoons each time) 2-3 times a week during this study.

You may receive up to 12 cycles of therapy. You may be taken off study early if the disease gets worse or intolerable side effects occur.

Once you go off study, you will have standard follow-up as is required by your primary physician.

This is an investigational study. 5-aza is approved by the FDA for MDS. VPA is approved by the FDA for epilepsy. Their use together in this study is experimental. Ara-C is approved for acute myelogenous leukemia. About 70 patients will take part in this study. All will be enrolled at M. D. Anderson.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have untreated AML, or untreated MDS with > 10% blasts in marrow or blood.
  2. They must be at least age 60.
  3. They must either have a serum creatinine > 1.9 mg/ml, a serum bilirubin > 1.9 mg/ml, or a Zubrod performance status of 3 or 4.
  4. Alternatively, they must not be candidates for protocols of higher priority.
  5. They must provide written consent.

Exclusion Criteria:

1) Must not have the cytogenetic abnormalities inv (16), t (16;16) t (8;21), or t (15;17). The relatively good prognoses of patients with these findings do not warrant use of 5 azacytidine, + valproic acid or low-dose ara-C (LDAC).

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00382590

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Guillermo Garcia-Manero, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00382590     History of Changes
Other Study ID Numbers: 2005-0177
Study First Received: September 27, 2006
Results First Received: August 13, 2009
Last Updated: August 1, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Acute Myelogenous Leukemia
AML
Myelodysplastic Syndrome
Leukemia
MDS
Azacytidine
5-Azacytidine
5-aza
Vidaza
5-AZC
AZA-CR
Ladakamycin
Ara-C
Cytarabine
Cytosar
DepoCyt
Cytosine arabinosine hydrochloride
Valproic Acid
VPA
Depakene

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Leukemia
Syndrome
Leukemia, Myeloid, Acute
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Neoplasms by Histologic Type
Disease
Pathologic Processes
Cytarabine
Azacitidine
Valproic Acid
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Anticonvulsants
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014