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

NCT ID: NCT00382590

Last Updated: 2012-08-07

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-08-31

Study Completion Date

2008-02-29

Brief Summary

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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.

Detailed Description

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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an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.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.

Conditions

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Acute Myelogenous Leukemia Myelodysplastic Syndrome Leukemia

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

5-Azacytidine

Intervention Type DRUG

75 mg/m\^2 daily for 7 days (days 1-7) via subcutaneous injection.

Valproic Acid (VPA)

Intervention Type DRUG

50 mg/m\^2 orally daily days 1-7.

Ara-C

Low-Dose Ara-C 20 mg twice daily subcutaneously for 10 days.

Group Type ACTIVE_COMPARATOR

Ara-C

Intervention Type DRUG

20 mg twice daily via subcutaneous injection for 10 days.

Interventions

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5-Azacytidine

75 mg/m\^2 daily for 7 days (days 1-7) via subcutaneous injection.

Intervention Type DRUG

Ara-C

20 mg twice daily via subcutaneous injection for 10 days.

Intervention Type DRUG

Valproic Acid (VPA)

50 mg/m\^2 orally daily days 1-7.

Intervention Type DRUG

Other Intervention Names

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Azacytidine 5-aza Vidaza 5-AZC AZA-CR Ladakamycin Cytarabine Cytosar DepoCyt Cytosine arabinosine hydrochloride VPA Depakene

Eligibility Criteria

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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).
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Guillermo Garcia-Manero, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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UT MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.mdanderson.org

UT MD Anderson Cancer Center website

Other Identifiers

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2005-0177

Identifier Type: -

Identifier Source: org_study_id