Deferasirox, Cholecalciferol, and Azacitidine in the Treatment of Newly Diagnosed AML Patients Over 65

Study Overview
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Brief Summary
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The purpose of this study is to find out if by giving a combination of 3 drugs the leukemia will go into complete remission (meaning the leukemia is completely gone), and to find out how long it stays away. The drugs used in this project are FDA approved and commercially available.

Detailed Description
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The majority of new cases of acute myeloid leukemia (AML) are diagnosed in patients older than 65 years of age. The median age of patients at time of diagnosis is 67 years. Standard therapies for AML often have significant toxicity and are poorly tolerated by this patient population. Treatment strategies for elderly patients with AML are limited. In those patients who do achieve complete remission, duration of remission tends to be short. Treatment at time of relapse is exceedingly difficult and outcomes are dismal. Thus, there is need for safer and more effective therapies for elderly patients with AML. This trial is a novel therapeutic combination of deferasirox (Exjade), cholecalciferol, and azacitidine in patients 65 years or older with newly diagnosed AML who are not fit for standard induction chemotherapy or hematopoietic stem-cell transplantation.

Official Title
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A Phase II Study Examining the Use of Deferasirox, Cholecalciferol, and Azacitidine in the Treatment of Newly Diagnosed Acute Myelogenous Leukemia (AML) in Elderly Patients

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Deferasirox
* Drug: Cholecalciferol
* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 65 or older (must have reached 65th birthday) Morphologically confirmed diagnosis of AML, excluding AML-M3 Must have a Zubrod performance status of 0-3 Exclusion Criteria: Patients with known HIV infection are excluded. If HIV infection is suspected based on clinical condition, testing may be performed at the discretion of treatment team, but is not mandated prior to enrollment. Patients with central nervous system involvement by AML are excluded Patients with history of an active cancer (except basal cell and squamous cell cancers of the skin) within the previous 2 years are excluded

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 89 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: Drug Treatment<br>Deferasirox (20mg/kg/day)on days 1-7 of protocol, repeated every four weeks for 8 cycles given PO Cholecalciferol(4,000 units/day), on days 1-7 of protocol, repeated every four weeks for 8 cycles given PO Azacitidine (75mg/m2 subcutaneous or IV administration) on days 1-7 of protocol, repeated every four weeks for 8 cycles given either subcutaneously or IV | Drug: Deferasirox<br>* Deferasirox (20mg/kg/day)on days 1-7 of protocol every 4 wks for 8 cycles PO<br>* Other names: Exjade;Drug: Cholecalciferol<br>* Cholecalciferol(4,000 units/day) on days 1-7 of protocol every 4 wks for 8 cycles PO<br>* Other names: Vitamin D;Drug: Azacitidine<br>* Azacitidine (75mg/m2 subcutaneous or IV administration) on days 1-7 of protocol 28 days for 32 wks<br>* Other names: Vidaza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate | The Complete Remission Rate for all evaluable patients will be reported for the following treatment: azacitadine, vitamin D, and deferasirox (Exjade). The proportion of patients experiencing per-protocol CR will be calculated with a 90% exact confidence interval. | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events | Characterization of the safety of an induction regimen of azacitidine in combination with vitamin D and deferasirox (Exjade). The proportion of patients experiencing severe adverse events, and the number of patients experiencing severe adverse events probably or definitely related to treatment will be determined. Adverse events will be tabulated by category and graded by NCI CTCAE version 4.0 | up to 5 years | 
| Survival | The overall survival and relapse-free survival functions. Product-limit (Kaplan-Meier) estimate of the survival functions will be estimated, with 90% confidence intervals. | up to 5 years | 
| Duration of Remission | The length of time for remission after achieving complete remission | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Azacitidine, Vidaza, Deferasirox, Exjade, Cholecalciferol, Vitamin D