Clofarabine vs Clofarabine in Plus With Low-Dose Ara-C in Previously Untreated Patients With Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS).

NCT ID: NCT00088218

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

95 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-07-31

Study Completion Date

2008-02-29

Brief Summary

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The goal of this clinical research study is to study how effective treatments with clofarabine alone and clofarabine given in combination with ara-C are in the treatment of leukemia and high-risk myelodysplastic syndrome (MDS) in patients who are 60 years or older. The safety of these treatments will also be compared.

Detailed Description

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Clofarabine is a chemotherapy drug that is designed to interfere with the growth and development of cancer cells. Ara-C is a chemotherapy drug which is approved for the treatment of AML and MDS. Although there is experience with the combination of both drugs, there have not been trials that explored the particular doses and schedule of clofarabine plus ara-C that you may receive.

Before you can start treatment on the 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 a complete medical history and physical exam. You will also be asked about what medications you are taking currently and about the level of your daily activities. About 2 tablespoons of blood will be collected for routine blood tests and to make sure you are not at increased risk for developing side effects.

Before your first treatment (usually within 14 days), you may have bone marrow samples collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. The procedure will be explained to you by your doctor and will require you to sign a separate consent document.

Early study results showed that there is clearly a better response with the combination treatment compared to the clofarabine alone treatment. Because of this, all participants in this study will now be assigned to the clofarabine plus ara-C group. You will receive clofarabine through a vein daily for 5 days in a row. In addition, you will receive injections of ara-C under the skin once a day for 14 days in a row. On those days when both clofarabine and ara-C are taken, the clofarabine will be given approximately 4 hours before the ara-C injections. You can be taught to give the ara-C injections to yourself. Each cycle may be repeated every 3 to 6 weeks. You will be required to record the injections in a medication diary.

Up to 2 of these cycles (for both groups) can be given at this dose schedule. If you show a response to treatment, you can continue with up to 12 cycles of therapy, during which clofarabine will be given for 3 days instead of 5 and ara-C for 7 days instead of 14. Maintenance courses may be given on average every 4 to 7 weeks.

Before every treatment course, you will have a physical exam including measurement of your weight and vital signs. You will also be asked how you are feeling and how you are able to go about your daily routine. At least once a week (more often if your doctor feels it is necessary), you will have blood samples (about 1-2 teaspoons) collected for routine lab tests. Around 3 weeks after your first treatment, you may have samples of bone marrow collected. After that, the bone marrow collections will be performed every 2 weeks (or more often if your doctor feels it is necessary). The bone marrow sample will be tested to evaluate the response of the disease to therapy.

You will need to stay in Houston for the first 4 weeks of treatment. After that, you have to return to Houston to receive the clofarabine treatment, but you can have check-up visits and blood tests with your local doctor. If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you.

After you finished your treatment, and as long you are participating on this study you will be scheduled every 3-6 months to check on the status of the disease and your overall health as long as you stay on the study. Once you are taken off the study, your doctor will decide how often you will have follow-up as part of your standard care.

This is an investigational study. Clofarabine is authorized by the Food and Drug Administration (FDA) for use in research only. Up to 108 participants will take part in this study. All will be enrolled at M. D. Anderson.

Conditions

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Acute Myeloid Leukemia Myelodysplastic Syndrome

Keywords

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Acute Myeloid Leukemia AML High-Risk Myelodysplastic Syndrome MDS Clofarabine Cytarabine ara-C

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Clofarabine

Clofarabine intravenous (IV) 30 mg/m\^2 daily times 5 days

Group Type ACTIVE_COMPARATOR

Clofarabine

Intervention Type DRUG

1-hour IV infusion 30 mg/m\^2 daily times 5 days (Days 1-5)

Clofarabine Plus Ara-C

Clofarabine IV 30 mg/m\^2 daily times 5 days + Ara-C 20 mg/m\^2 subcutaneously daily times 14 days.

Group Type ACTIVE_COMPARATOR

Clofarabine

Intervention Type DRUG

1-hour IV infusion 30 mg/m\^2 daily times 5 days (Days 1-5)

Ara-C

Intervention Type DRUG

20 mg/m\^2 subcutaneously daily times 14 days (Days 1-14). On Days 1 to 5 of each course, clofarabine will precede injection of ara-C by approximately 4 hours (+/- 1 hour).

Interventions

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Clofarabine

1-hour IV infusion 30 mg/m\^2 daily times 5 days (Days 1-5)

Intervention Type DRUG

Ara-C

20 mg/m\^2 subcutaneously daily times 14 days (Days 1-14). On Days 1 to 5 of each course, clofarabine will precede injection of ara-C by approximately 4 hours (+/- 1 hour).

Intervention Type DRUG

Other Intervention Names

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Clolar Clofarex Cytarabine Cytosar DepoCyt Cytosine arabinosine hydrocloride

Eligibility Criteria

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Inclusion Criteria

* Previously untreated AML and high-risk MDS ( \> 10% blasts, or International Prognostic Scoring System (IPSS) intermediate-2). Prior therapy with hydroxyurea, single agent chemotherapy (e.g. decitabine), hematopoietic growth factors, biological or "targeted" therapies are allowed.
* Age \> 60 years.
* Eastern Cooperative Oncology Group (ECOG) performance status \</= 2.
* Sign a written informed consent form.
* Adequate liver function (total bilirubin \< 2mg/dL,serum glutamic pyruvic transaminase (SGPT) or Serum glutamic oxaloacetic transaminase (SGOT) \< x 4 upper limit of normal (ULN)) and renal function (serum creatinine \< 2mg/dL).

Exclusion Criteria

* Patients with \>= New York Heart Association (NYHA) grade 3 heart disease as assessed by history and/or physical examination.
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stefan Faderl, MD

Role: STUDY_CHAIR

The University of Texas MD Anderson Cancer Center

Locations

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M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. doi: 10.1182/blood-2007-11-124602. Epub 2008 Jun 18.

Reference Type DERIVED
PMID: 18565853 (View on PubMed)

Related Links

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http://www.mdanderson.org

M.D. Anderson Cancer Center's website

Other Identifiers

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2004-0183

Identifier Type: -

Identifier Source: org_study_id