EMIX: Exploratory Multi-centre Trial In Patients With ET Treated With XAGRID®

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01352585
• Collaborator: (none)
• Enrollment: 47
• Locations: 10
• Actual Duration (Months): 26.1
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is hypothesis-generating to explore the impact of JAK2 (V617F) mutation status on the treatment response to anagrelide hydrochloride

Condition or Disease	Intervention/Treatment	Phase
Essential Thrombocythemia (ET)	Drug: Anagrelide hydrochloride

Study Design

• Study Type: Observational
• Actual Enrollment: 47 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: An Exploratory, Observational, Multicentre Study to Investigate the Impact of the Presence of JAK2 (V617F) Mutation on Treatment Response in Patients With Essential Thrombocythaemia Treated With XAGRID® (Anagrelide Hydrochloride)
• Actual Study Start Date: Jul 19, 2011
• Actual Primary Completion Date: Sep 19, 2013
• Actual Study Completion Date: Sep 19, 2013

Arms and Interventions

Arm	Intervention/Treatment
JAK2 Positive Participants	Drug: Anagrelide hydrochloride; 0.5 mg hard capsules, dosing decisions will be made by the treating physician; Other Names: Xagrid
JAK2 Negative Participants	Drug: Anagrelide hydrochloride; 0.5 mg hard capsules, dosing decisions will be made by the treating physician; Other Names: Xagrid

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Platelet Count ≤600x10^9/L After 12 Months [1 year]

   A platelet count of ≤600x10^9/L after 12 months is considered at least a partial response.

Secondary Outcome Measures

1. Number of Patients With Platelet Count ≤400x10^9/L After 12 Months [1 year]

   A platelet count of ≤400x10^9/L after 12 months is considered a complete response.

2. Platelet Count [1 year]

3. Red Blood Cell (RBC) Count [1 year]

4. White Blood Cell (WBC) Count [1 year]

5. Differential WBC Count - Neutrophils, Lymphocytes, Monocytes, and Basophils. [1 year]

6. Differential WBC Count - Eosinophils [1 year]

7. Hemoglobin Concentration [1 year]

8. Hematocrit Level [1 year]

   The proportion of the volume of red blood cells to the total volume of blood.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients must be able to understand and willing to participate in the study, and provide a personally dated and signed written informed consent form.

2. Patients must have a confirmed diagnosis of ET according to the World health Organisation's criteria.

3. ET patients who are uncontrolled, in the Investigator's opinion, by first-line (or previous) cytoreductive treatment for efficacy or tolerance reasons.

4. Patients who have either commenced treatment with anagrelide hydrochloride in the last 7 days or for whom a decision has been documented to commence treatment with anagrelide hydrochloride

Exclusion Criteria:

1. Patients for whom treatment with anagrelide hydrochloride is contraindicated, according to the current XAGRID SmPC.

2. Known or suspected intolerance or hypersensitivity to the product, closely related compounds, or any of the stated ingredients.

3. Patients participating in an interventional research study.

4. Patients on combination therapy or for whom there is an intention to treat with other cytoreductive agents e.g., hydroxyurea, interferon. Patients can however use aspirin and other anti-aggregatory products at the Investigator's discretion.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Azienda Ospedaliera Policlinico di Bari	Bari		Italy
2	Istituto Seragnoli-Policlinico S.Orsola-Malpighi	Bologna		Italy
3	A.O. Spedali Civili di Brescia	Brescia		Italy
4	Azienda Ospedaliero-Universitaria Careggi	Firenze		Italy
5	Ospedale San Martino	Genova		Italy
6	Fondazione IRCCS Ca' Granda	Milan		Italy	20125
7	Azienda Ospedaliera Universitaria "Federico II"	Napoli		Italy	80131
8	Ospedale Maggiore della Carita	Novara		Italy
9	Policlinico A. Gemelli	Roma		Italy
10	Padiglione ex-oncologico Ospedale S.Maria	Terni		Italy

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01352585
• Other Study ID Numbers: SPD422-703
• First Posted: May 12, 2011
• Last Update Posted: Jul 30, 2021
• Last Verified: Jul 1, 2021

• Additional relevant MeSH terms: Thrombocytosis; Thrombocythemia, Essential; Anagrelide

Study Results

Participant Flow

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician
Period Title: Overall Study
STARTED	23	24
COMPLETED	15	21
NOT COMPLETED	8	3

Baseline Characteristics

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants	Total
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Total of all reporting groups
Overall Participants	23	24	47
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.4 (14.00)	58.6 (15.94)	58.0 (14.87)
Sex: Female, Male (Count of Participants)
Female	14 60.9%	14 58.3%	28 59.6%
Male	9 39.1%	10 41.7%	19 40.4%
Region of Enrollment (Count of Participants)
Italy	23 100%	24 100%	47 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Platelet Count ≤600x10^9/L After 12 Months
Description	A platelet count of ≤600x10^9/L after 12 months is considered at least a partial response.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) in each JAK2 status group who had a viable platelet sample during the 12-month follow-up window. For this Outcome Measure 35 patients in the FAS had a viable laboratory sample.

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician
Measure Participants	14	21
Number [participants]	12 52.2%	14 58.3%

2. Secondary Outcome

Title	Number of Patients With Platelet Count ≤400x10^9/L After 12 Months
Description	A platelet count of ≤400x10^9/L after 12 months is considered a complete response.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) in each JAK2 status group who had a viable platelet sample during the 12-month follow-up window. For this Outcome Measure 35 patients in the FAS had a viable laboratory sample.

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician
Measure Participants	14	21
Number [participants]	7 30.4%	8 33.3%

3. Secondary Outcome

Title	Platelet Count
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) in each JAK2 status group who had a viable platelet sample during the 12-month follow-up window. For this Outcome Measure 28 patients in the FAS had a viable laboratory sample.

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician.
Measure Participants	11	17
Mean (Standard Deviation) [Platelets (x10^9/L)]	458.9 (163.25)	503.0 (254.04)

4. Secondary Outcome

Title	Red Blood Cell (RBC) Count
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set (SAS) consisted of all subjects enrolled in the study who took at least 1 dose of anagrelide hydrochloride. 27 patients in the SAS met this requirement and had a viable laboratory sample.

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician
Measure Participants	11	16
Mean (Standard Deviation) [RBC Count (x10^12/L)]	4.85 (0.430)	4.24 (0.797)

5. Secondary Outcome

Title	White Blood Cell (WBC) Count
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) in each JAK2 status group who had a viable platelet sample during the 12-month follow-up window. For this Outcome Measure 28 patients in the FAS had a viable laboratory sample.

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician
Measure Participants	11	17
Mean (Standard Deviation) [WBC Count (x10^9/L)]	7.75 (1.317)	8.77 (3.770)

6. Secondary Outcome

Title	Differential WBC Count - Neutrophils, Lymphocytes, Monocytes, and Basophils.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) in each JAK2 status group who had a viable platelet sample during the 12-month follow-up window. For this Outcome Measure 28 patients in the FAS had a viable laboratory sample.

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician
Measure Participants	11	17
Neutrophils	62.05 (4.429)	60.07 (13.515)
Lymphocytes	27.53 (4.412)	28.76 (12.381)
Monocytes	6.50 (2.235)	7.21 (2.680)
Basophils	1.75 (2.425)	0.81 (0.486)

7. Secondary Outcome

Title	Differential WBC Count - Eosinophils
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) in each JAK2 status group who had a viable platelet sample during the 12-month follow-up window. For this Outcome Measure 27 patients in the FAS had a viable laboratory sample.

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician
Measure Participants	11	16
Mean (Standard Deviation) [percent]	2.95 (1.958)	2.77 (1.906)

8. Secondary Outcome

Title	Hemoglobin Concentration
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set (SAS) consisted of all subjects enrolled in the study who took at least 1 dose of anagrelide hydrochloride. 28 patients in the SAS had a viable laboratory sample.

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician
Measure Participants	11	17
Mean (Standard Deviation) [g/L]	133.6 (13.09)	120.2 (16.85)

9. Secondary Outcome

Title	Hematocrit Level
Description	The proportion of the volume of red blood cells to the total volume of blood.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set (SAS) consisted of all subjects enrolled in the study who took at least 1 dose of anagrelide hydrochloride. 27 patients in the SAS had a viable laboratory sample.

Arm/Group Title	JAK2 Positive Participants	JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician
Measure Participants	11	16
Mean (Standard Deviation) [Hematocrit (fraction of 1)]	0.412 (0.0335)	0.367 (0.0608)

Adverse Events

Arm/Group Title	JAK2 Positive Participants		JAK2 Negative Participants
Arm/Group Description	Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician		Anagrelide hydrochloride: 0.5 mg hard capsules, dosing decisions will be made by the treating physician
All Cause Mortality
	JAK2 Positive Participants		JAK2 Negative Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	JAK2 Positive Participants		JAK2 Negative Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	JAK2 Positive Participants		JAK2 Negative Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/23 (26.1%)		9/24 (37.5%)
Blood and lymphatic system disorders
anemia	1/23 (4.3%)	1	2/24 (8.3%)	3
Cardiac disorders
Palpitations	1/23 (4.3%)	1	1/24 (4.2%)	1
Tachycardia	1/23 (4.3%)	1	1/24 (4.2%)	1
Eye disorders
Scotoma	0/23 (0%)		1/24 (4.2%)	1
Gastrointestinal disorders
Diarrhea	0/23 (0%)		1/24 (4.2%)	1
Metabolism and nutrition disorders
Hyperuricemia	0/23 (0%)		1/24 (4.2%)	1
Nervous system disorders
Headache	2/23 (8.7%)	2	4/24 (16.7%)	4
Presyncope	1/23 (4.3%)	1	0/24 (0%)	1
Skin and subcutaneous tissue disorders
Dermatits	1/23 (4.3%)	1	0/24 (0%)	1
Pruritus	0/23 (0%)		1/24 (4.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.