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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Deferasirox; Drug: Cholecalciferol; Drug: Azacitidine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Cardinal Bernardin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 89 years (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Drug Treatment; 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; Deferasirox (20mg/kg/day)on days 1-7 of protocol every 4 wks for 8 cycles PO; Other Names: Exjade; Drug: Cholecalciferol; Cholecalciferol(4,000 units/day) on days 1-7 of protocol every 4 wks for 8 cycles PO; Other Names: Vitamin D; Drug: Azacitidine; Azacitidine (75mg/m2 subcutaneous or IV administration) on days 1-7 of protocol 28 days for 32 wks; Other Names: Vidaza

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Elizabeth Henry
• Investigators: Principal Investigator: Elizabeth Henry, MD, Faculty

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2013
• Primary Completion (ACTUAL): November 1, 2016
• Study Completion (ACTUAL): November 1, 2016

Study Registration Dates

• First Submitted: September 26, 2013
• First Submitted That Met QC Criteria: January 13, 2015
• First Posted (ESTIMATE): January 19, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Vitamin D; Deferasirox; Azacitidine; Exjade; Cholecalciferol; Vidaza
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Vitamin D; Cholecalciferol; Azacitidine; Deferasirox
• Other Study ID Numbers: 204961

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share individuals participant data.