Arsenic Trioxide in Combination With Cytarabine in Patients With High-risk MDS and Poor-prognosis AML

Study Overview
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Brief Summary
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The purpose of this study is to find out the effectiveness and side effects of arsenic trioxide in combination with low-dose ara-C.

Detailed Description
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This is an open-label, single institution, dose-escalation study of low-dose cytosine arabinoside and arsenic trioxide. Patients will receive a fixed dose of arsenic trioxide administered 0.25mg/kg/day on days 1-5 and 8-12 and ara-C administered at 5, 7.5, or 10 mg/m2 SC BID days 1-14 in repeated cycles of 2 weeks on therapy and 2 weeks off therapy in a standard dose escalation design (1 cycle = 2 weeks on therapy + 2 weeks off therapy).

Official Title
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Phase I/II Study of Arsenic Trioxide in Combination With Cytosine Arabinoside in Patients With High-risk Myelodysplastic Syndrome and Poor-prognosis Acute Myelogenous Leukemia

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Arsenic Trioxide (Tricenox)
* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of high-risk MDS (IPSS int-2). No prior cytotoxic therapy for MDS or AML (patients may have received prior therapy with hematopoietic growth factors, immunomodulatory agents or 5-azacitidine). Exclusion Criteria: Pregnant or lactating women. Absolute QT interval >460 msec in the presence of serum potassium and magnesium values within the normal range. Concurrent treatment with maintenance therapy, cytotoxic chemotherapy, radiation, or investigational agents. Uncontrolled or severe cardiovascular or pulmonary disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Patients<br>Arsenic trioxide [TrisenoxTM Injection], 0.25mg/kg/dose administered intravenously over 1 to 4 hours | Drug: Arsenic Trioxide (Tricenox)<br> <br> Drug: Cytarabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of cytosine arabinoside in combination with ATO 0.25mg/kg/day IV for 10 days on therapy followed by 14 days off therapy in patients with high-risk MDS and poor-prognosis AML. |  | 10 days on therapy followed by 14 days off therapy in patients with high-risk MDS and poor-prognosis AML | 
| To characterize the safety and tolerability of the combination of ATO and low-dose ara-C, including acute and chronic toxicities. |  | 4 weeks after the last study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the CR and PR rates in patients with high-risk MDS and poor-prognosis AML treated with the combination of ATO and low-dose ara-C. |  | 4 weeks after the last study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndrome