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

• Sponsor: Elizabeth Henry (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02341495
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arm: 1
• Actual Duration (Months): 45
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Deferasirox; Drug: Cholecalciferol; Drug: Azacitidine	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Complete Remission Rate [up to 5 years]

   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.

Secondary Outcome Measures

1. Number of Patients With Adverse Events [up to 5 years]

   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

2. Survival [up to 5 years]

   The overall survival and relapse-free survival functions. Product-limit (Kaplan-Meier) estimate of the survival functions will be estimated, with 90% confidence intervals.

3. Duration of Remission [up to 5 years]

   The length of time for remission after achieving complete remission

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loyola University Cardinal Bernardin Cancer Center	Maywood	Illinois	United States	60153

Sponsors and Collaborators

• Elizabeth Henry

Investigators

• Principal Investigator: Elizabeth Henry, MD, Faculty

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elizabeth Henry, Faculty, Loyola University
• ClinicalTrials.gov Identifier: NCT02341495
• Other Study ID Numbers: 204961
• First Posted: Jan 19, 2015
• Last Update Posted: Feb 27, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Elizabeth Henry, Faculty, Loyola University: Azacitidine; Vidaza; Deferasirox; Exjade; Cholecalciferol; Vitamin D
• Additional relevant MeSH terms: Leukemia; Vitamin D; Cholecalciferol; Azacitidine; Deferasirox

Study Results

Participant Flow

Arm/Group Title	Drug Treatment
Arm/Group Description	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 Deferasirox: Deferasirox (20mg/kg/day)on days 1-7 of protocol every 4 wks for 8 cycles PO Cholecalciferol: Cholecalciferol(4,000 units/day) on days 1-7 of protocol every 4 wks for 8 cycles PO Azacitidine: Azacitidine (75mg/m2 subcutaneous or IV administration) on days 1-7 of protocol 28 days for 32 wks
Period Title: Overall Study
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Drug Treatment
Arm/Group Description	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 Deferasirox: Deferasirox (20mg/kg/day)on days 1-7 of protocol every 4 wks for 8 cycles PO Cholecalciferol: Cholecalciferol(4,000 units/day) on days 1-7 of protocol every 4 wks for 8 cycles PO Azacitidine: Azacitidine (75mg/m2 subcutaneous or IV administration) on days 1-7 of protocol 28 days for 32 wks
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	4 100%
Sex: Female, Male (Count of Participants)
Female	3 75%
Male	1 25%
Race/Ethnicity, Customized (Count of Participants)
White	4 100%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Complete Remission Rate
Description	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.
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

No patients were analyzed as study was terminated early due to low accrual. Therefore, data necessary for planned analyses were not collected.

Arm/Group Title	Drug Treatment
Arm/Group Description	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 Deferasirox: Deferasirox (20mg/kg/day)on days 1-7 of protocol every 4 wks for 8 cycles PO Cholecalciferol: Cholecalciferol(4,000 units/day) on days 1-7 of protocol every 4 wks for 8 cycles PO Azacitidine: Azacitidine (75mg/m2 subcutaneous or IV administration) on days 1-7 of protocol 28 days for 32 wks
Measure Participants	0

2. Secondary Outcome

Title	Number of Patients With Adverse Events
Description	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
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

No patients were analyzed as study was terminated early due to low accrual. Therefore, data necessary for planned analyses were not collected.

Arm/Group Title	Drug Treatment
Arm/Group Description	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 Deferasirox: Deferasirox (20mg/kg/day)on days 1-7 of protocol every 4 wks for 8 cycles PO Cholecalciferol: Cholecalciferol(4,000 units/day) on days 1-7 of protocol every 4 wks for 8 cycles PO Azacitidine: Azacitidine (75mg/m2 subcutaneous or IV administration) on days 1-7 of protocol 28 days for 32 wks
Measure Participants	0

3. Secondary Outcome

Title	Survival
Description	The overall survival and relapse-free survival functions. Product-limit (Kaplan-Meier) estimate of the survival functions will be estimated, with 90% confidence intervals.
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

No patients were analyzed as study was terminated early due to low accrual. Therefore, data necessary for planned analyses were not collected.

Arm/Group Title	Drug Treatment
Arm/Group Description	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 Deferasirox: Deferasirox (20mg/kg/day)on days 1-7 of protocol every 4 wks for 8 cycles PO Cholecalciferol: Cholecalciferol(4,000 units/day) on days 1-7 of protocol every 4 wks for 8 cycles PO Azacitidine: Azacitidine (75mg/m2 subcutaneous or IV administration) on days 1-7 of protocol 28 days for 32 wks
Measure Participants	0

4. Secondary Outcome

Title	Duration of Remission
Description	The length of time for remission after achieving complete remission
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

No patients were analyzed as study was terminated early due to low accrual. Therefore, data necessary for planned analyses were not collected.

Arm/Group Title	Drug Treatment
Arm/Group Description	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 Deferasirox: Deferasirox (20mg/kg/day)on days 1-7 of protocol every 4 wks for 8 cycles PO Cholecalciferol: Cholecalciferol(4,000 units/day) on days 1-7 of protocol every 4 wks for 8 cycles PO Azacitidine: Azacitidine (75mg/m2 subcutaneous or IV administration) on days 1-7 of protocol 28 days for 32 wks
Measure Participants	0

Adverse Events

Time Frame	Adverse event data were collected for 45 months
Arm/Group Title	Drug Treatment
Arm/Group Description	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 Deferasirox: Deferasirox (20mg/kg/day)on days 1-7 of protocol every 4 wks for 8 cycles PO Cholecalciferol: Cholecalciferol(4,000 units/day) on days 1-7 of protocol every 4 wks for 8 cycles PO Azacitidine: Azacitidine (75mg/m2 subcutaneous or IV administration) on days 1-7 of protocol 28 days for 32 wks
All Cause Mortality
	Drug Treatment
	Affected / at Risk (%)	# Events
Total	2/4 (50%)
Serious Adverse Events
	Drug Treatment
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Drug Treatment
	Affected / at Risk (%)	# Events
Total	0/4 (0%)

Limitations/Caveats

There are no limitations or caveats to report as the study was terminated early due to low accrual.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.