Combination Study of Deferasirox and Erythropoietin in Patients With Low- and Int-1-risk Myelodysplastic Syndrome.

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01868477
• Collaborator: (none)
• Enrollment: 28
• Locations: 30
• Arms: 2
• Actual Duration (Months): 38.2
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary purpose of this trial was is to assess the effect of treatment with deferasirox combined with erythropoietin vs. erythropoietin alone on erythropoiesis in patients with low- and int-1-risk myelodysplastic syndrome. The addition of deferasirox to erythropoietin can lead to a potential synergism with the reduction of reactive oxygen species, through both the NF-kB pathway and the control of free toxic iron. This may create a better environment in the bone marrow for a better response with erythropoietin.

This study was designed to test in a prospective way the combination of deferasirox with erythropoietin in terms of their effect on hematopoiesis.

Condition or Disease	Intervention/Treatment	Phase
Low and Int 1-risk Myelodysplastic Syndrome	Drug: Deferasirox DFX, DT; Drug: Erythropoietin alpha; Drug: Deferasirox DFX, FCT	Phase 2

Detailed Description

This study did not meet the original enrollment objective of 60 patients and was terminated without extending enrollment past original planned LPFV of 31-Oct-2016.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Phase II, Randomized, Pilot Study to Assess the Effect in Term of Erythroid Improvement of Deferasirox Combined With Erythropoietin Compared to Erythropoietin Alone in Patients With low-and Int-1-risk Myelodysplastic Syndrome.
• Actual Study Start Date: Jan 28, 2014
• Actual Primary Completion Date: Mar 22, 2017
• Actual Study Completion Date: Apr 5, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erythropoietin alpha Patients will receive erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement is inadequate, dose will be escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement in inadequate, patients will be switched to the combination arm. At any time when erythroid response is achieved, erythropoietin treatment will be stopped until end of study.	Drug: Erythropoietin alpha
Experimental: Deferasirox + Erythropoietin alpha Patients will receive deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet (FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement is inadequate, erythropoietin dose will be escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement in inadequate, patients will be discontinued from the study. At any time when erythroid response is achieved, erythropoietin treatment will be stopped until end of study. Patients will continue deferasirox treatment.	Drug: Deferasirox DFX, DT; provided as dispersible tablets for oral use in 125 and 250, 500 mg; Drug: Deferasirox DFX, FCT; provided as film-coated tablet for oral use in 90, 180, 360 mg strengths

Outcome Measures

Primary Outcome Measures

1. Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set) [Baseline up to 12 weeks]

   Difference in percentage of patients achieving an erythroid response within 12 weeks of treatment between the two arms according to modified IWG 2006 criteria increase in hemoglobin (Hb) ≥ 1.5 g/dL. Erythroid response is defined as the increase in Hb from baseline ≥ 1.5 g/dL. Patients achieving erythroid response at least once within 12 weeks were considered responders

Secondary Outcome Measures

1. Absolute Change From Baseline to Post-baseline Value for Hemoglobin(g/dL)(Full Analysis Set) [Baseline up to 24 weeks]

   Hematological response criteria defined as: Erythroid response: hemoglobin (Hb) increase from baseline >= 1.5 g/dL (baseline < 11 g/dL), neutrophil response: increase from baseline >= 100% and increase > 0.5 × 10^9/L (baseline <1 × 10^9/L), platelet response: increase from baseline >= 30 × 10^9/L (baseline <100 × 10^9/L) according to modified IWG 2006 criteria

2. Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) [Baseline up to 24 weeks]

   Percentage of participants achieving an hematologic improvement defined as: neutrophil improvement: increase from baseline >0.5 × 10^9/L (baseline = 1.0 × 10^9/L ), platelet improvement: increase from baseline ≥ 30 × 10^9/L (baseline = 100 × 10^9/L), hemoglobin improvement: Hb increase from baseline ≥ 1 g/dL (baseline<11 g/dL)

3. Absolute Change in Hemoglobin Values up to 24 Weeks [Baseline up to 24 weeks]

   Absolute change in hemoglobin values for patients showing improvement: Hemoglobin improvement Hb increase from baseline ≥ 1 g/dL (baseline<11 g/dL)

4. Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks [Baseline up to 24 weeks]

   Absolute change in platelets and neutrophil levels for participants showing improvement: neutrophil improvement: increase from baseline >0.5 × 10^9/L (baseline = 1.0 × 10^9/L ), platelet improvement: increase from baseline ≥ 30 × 10^9/L (baseline = 100 × 10^9/L)

5. Summary of Erythroid Response in Participants Randomized to EPO Alone at Baseline and Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set) [Week 13 up to 24 weeks]

   Erythroid response: hemoglobin increase from baseline > = 1.5 g/dL (baseline <11 g/dL)

6. Summary of Erythroid Response Within 24 Weeks in Participants Randomized to EPO at Baseline and Not Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set) [baseline up to 24 weeks]

   Erythroid response: hemoglobin increase from baseline > = 1.5 g/dL (baseline <11 g/dL). Percentages are based on N. Confidence intervals are calculated using Clopper-Pearson method. Hemoglobin value is at time of first response

7. Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) [Baseline up to 24 weeks]

   Absolute change in serum ferritin from baseline

8. Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) [Baseline up to 24 weeks]

   Absolute change in serum ferritin from baseline

9. Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) [Baseline up 24 weeks]

   Absolute change in serum ferritin from baseline

10. Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) [Baseline up to 24 weeks]

    This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy.

11. Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) [Baseline up to 24 weeks]

    This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy.

12. Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) [Baseline up to 24 weeks]

    This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy. The time-course of Hb and its absolute changes from baseline was summarized by descriptive statistics by visit and erythroid response. Patients randomized to EPO and not switching after 12 weeks to EPO+DFX would consist of only responders.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Patients who had low- and Int-1-risk myelodysplastic syndrome

• Documented diagnosis of the following:

Myelodysplastic syndrome that lasted ≥ 3 months and < 3 years Disease must not have been secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases

• A hemoglobin < 10 g/dL and ≥ 8 g/dL

• History of transfusions < 10 RBC units and must not have been RBC transfusion dependent

• 300 ng/mL < serum ferritin < 1,500 ng/mL (Values within 10% difference above 1500 ng/ml or 10% difference below 300 ng/ml could have been accepted at the investigator's discretion.

• Endogenous erythropoietin levels < 500 units/L

• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)

• Creatinine clearance above the concentration limit in locally approved prescribing information (PI). Patients with creatinine clearance between 40 and less than 60 mL/min, who did not present with additional risk factors that might impair renal function, were eligible at the discretion of the investigator

Key Exclusion Criteria:

• Patients who had MDS with isolated del(5q)

• Patients who had received prior EPO treatment or other recombinant growth factors regardless of the outcome (Patient who had received prior EPO treatment or other recombinant growth factors for less than 4 weeks and not within 3 months before screening without a documented response are allowed)

• Patients who had received steroids or immunosuppressive therapy for the improvement of hematological parameters (stable steroid treatment for adrenal failure or chronic medical conditions, and intermittent dexamethasone as antiemetics were allowed).

• B12 and folate deficient patients with and without clinical symptoms (patients were rescreened after successful therapy of B12 and folate deficiency)

• Uncontrolled seizures or uncontrolled hypertension

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Oran		Algeria	31000
2	Novartis Investigative Site	Sidi Bel abbes		Algeria	22000
3	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1425DND
4	Novartis Investigative Site	La Plata	Buenos Aires	Argentina	B1900AWT
5	Novartis Investigative Site	Vancouver	British Columbia	Canada	V6Z1Y6
6	Novartis Investigative Site	Hamilton	Ontario	Canada	L8V 5C2
7	Novartis Investigative Site	Toronto	Ontario	Canada	M4N 3M5
8	Novartis Investigative Site	Beijing	Beijing	China	100730
9	Novartis Investigative Site	Guangzhou	Guangdong	China	51000
10	Novartis Investigative Site	Nanjing	Jiangsu	China
11	Novartis Investigative Site	Chengdu	Sichuan	China	610041
12	Novartis Investigative Site	Hangzhou	Zhejiang	China	310003
13	Novartis Investigative Site	Shanghai		China	200025
14	Novartis Investigative Site	Berlin		Germany	12203
15	Novartis Investigative Site	Dresden		Germany	01307
16	Novartis Investigative Site	Duesseldorf		Germany	40225
17	Novartis Investigative Site	Lütten-Klein		Germany	18107
18	Novartis Investigative Site	Wuerzburg		Germany	97080
19	Novartis Investigative Site	Cagliari	CA	Italy	09126
20	Novartis Investigative Site	Reggio Calabria	RC	Italy	89124
21	Novartis Investigative Site	Roma	RM	Italy	00161
22	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	06351
23	Novartis Investigative Site	Badalona	Catalunya	Spain	08916
24	Novartis Investigative Site	Girona	Catalunya	Spain	17007
25	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
26	Novartis Investigative Site	Gothenburg		Sweden	413 45
27	Novartis Investigative Site	Linköping		Sweden	SE-581 85
28	Novartis Investigative Site	Lulea		Sweden	SE 971 80
29	Novartis Investigative Site	Stockholm		Sweden	SE-141 86
30	Novartis Investigative Site	Oldham	Lancashire	United Kingdom	OL1 2JH

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Aug 6, 2015
• Statistical Analysis Plan - Jun 12, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01868477
• Other Study ID Numbers: CICL670A2421
• First Posted: Jun 4, 2013
• Last Update Posted: Oct 31, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Novartis Pharmaceuticals: myelodysplastic syndrome; MDS; myelodysplasia; blood disorder; cytopenias; low blood counts; progressive bone marrow failure; adult; ICL570; deferasirox; erythropoietin; erythropoiesis; NF-kB pathway; hematopoiesis.
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Epoetin Alfa; Deferasirox

Study Results

Participant Flow

Pre-assignment Detail	Twenty-three patients were randomized into the trial

Arm/Group Title	Erythropoietin Alpha	Deferasirox + Erythropoietin Alpha
Arm/Group Description	Starting dose was erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were switched to the combination arm. At any time when erythroid response was achieved, erythropoietin treatment was stopped until end of study.	Starting dose was deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, erythropoietin dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were discontinued from the study. At any time when erythroid response was achieved, erythropoietin treatment was stopped study and Deferasirox treatment was continued until end of study
Period Title: Overall Study
STARTED	12	11
Switched to EPO+DFX	5	0
Not Switched to EPO+DFX	7	0
COMPLETED	8	6
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Erythropoietin Alpha	Deferasirox + Erythropoietin Alpha	Total
Arm/Group Description	Starting dose was erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were switched to the combination arm. At any time when erythroid response was achieved, erythropoietin treatment was stopped until end of study.	Starting dose was deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, erythropoietin dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were discontinued from the study. At any time when erythroid response was achieved, erythropoietin treatment was stopped study and Deferasirox treatment was continued until end of study	Total of all reporting groups
Overall Participants	12	11	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.5 (5.84)	71.1 (7.54)	72.9 (6.77)
Sex: Female, Male (Count of Participants)
Female	8 66.7%	5 45.5%	13 56.5%
Male	4 33.3%	6 54.5%	10 43.5%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	8 66.7%	7 63.6%	15 65.2%
Asian	4 33.3%	4 36.4%	8 34.8%

Outcome Measures

1. Primary Outcome

Title	Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set)
Description	Difference in percentage of patients achieving an erythroid response within 12 weeks of treatment between the two arms according to modified IWG 2006 criteria increase in hemoglobin (Hb) ≥ 1.5 g/dL. Erythroid response is defined as the increase in Hb from baseline ≥ 1.5 g/dL. Patients achieving erythroid response at least once within 12 weeks were considered responders
Time Frame	Baseline up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erythropoietin Alpha	Deferasirox + Erythropoietin Alpha
Arm/Group Description	Starting dose was erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were switched to the combination arm. At any time when erythroid response was achieved, erythropoietin treatment was stopped until end of study.	Starting dose was deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, erythropoietin dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were discontinued from the study. At any time when erythroid response was achieved, erythropoietin treatment was stopped study and Deferasirox treatment was continued until end of study
Measure Participants	12	11
Number (95% Confidence Interval) [percentage of participants]	41.7 347.5%	27.3 248.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythropoietin Alpha, Deferasirox + Erythropoietin Alpha
	Comments
	Type of Statistical Test	Other
	Comments	difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.4
	Confidence Interval	(2-Sided) 95%; -24.0 to 48.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Absolute Change From Baseline to Post-baseline Value for Hemoglobin(g/dL)(Full Analysis Set)
Description	Hematological response criteria defined as: Erythroid response: hemoglobin (Hb) increase from baseline >= 1.5 g/dL (baseline < 11 g/dL), neutrophil response: increase from baseline >= 100% and increase > 0.5 × 10^9/L (baseline <1 × 10^9/L), platelet response: increase from baseline >= 30 × 10^9/L (baseline <100 × 10^9/L) according to modified IWG 2006 criteria
Time Frame	Baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erythropoietin Alpha	Deferasirox + Erythropoietin Alpha
Arm/Group Description	Starting dose was erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were switched to the combination arm. At any time when erythroid response was achieved, erythropoietin treatment was stopped until end of study.	Starting dose was deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, erythropoietin dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were discontinued from the study. At any time when erythroid response was achieved, erythropoietin treatment was stopped study and Deferasirox treatment was continued until end of study
Measure Participants	12	11
Mean (Standard Deviation) [g/dL]	1.8 (0.21)	2.1 (0.61)

3. Secondary Outcome

Title	Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set)
Description	Percentage of participants achieving an hematologic improvement defined as: neutrophil improvement: increase from baseline >0.5 × 10^9/L (baseline = 1.0 × 10^9/L ), platelet improvement: increase from baseline ≥ 30 × 10^9/L (baseline = 100 × 10^9/L), hemoglobin improvement: Hb increase from baseline ≥ 1 g/dL (baseline<11 g/dL)
Time Frame	Baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

Number of patients who met criteria varied across parameters

Arm/Group Title	Erythropoietin Alpha	Deferasirox + Erythropoietin Alpha
Arm/Group Description	Starting dose was erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were switched to the combination arm. At any time when erythroid response was achieved, erythropoietin treatment was stopped until end of study.	Starting dose was deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, erythropoietin dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were discontinued from the study. At any time when erythroid response was achieved, erythropoietin treatment was stopped study and Deferasirox treatment was continued until end of study
Measure Participants	12	11
Hematologic improvement	100 833.3%	45.5 413.6%
Neutropil improvement	66.7 555.8%	80.0 727.3%
Platelet improvement	50.0 416.7%	80.0 727.3%
Hemoglobin improvement	66.7 555.8%	60.0 545.5%

4. Secondary Outcome

Title	Absolute Change in Hemoglobin Values up to 24 Weeks
Description	Absolute change in hemoglobin values for patients showing improvement: Hemoglobin improvement Hb increase from baseline ≥ 1 g/dL (baseline<11 g/dL)
Time Frame	Baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erythropoietin Alpha	Deferasirox + Erythropoietin Alpha
Arm/Group Description	Starting dose was erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were switched to the combination arm. At any time when erythroid response was achieved, erythropoietin treatment was stopped until end of study.	Starting dose was deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, erythropoietin dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were discontinued from the study. At any time when erythroid response was achieved, erythropoietin treatment was stopped study and Deferasirox treatment was continued until end of study
Measure Participants	12	11
Mean (Standard Deviation) [g/dL]	1.3 (0.37)	1.4 (0.55)

5. Secondary Outcome

Title	Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks
Description	Absolute change in platelets and neutrophil levels for participants showing improvement: neutrophil improvement: increase from baseline >0.5 × 10^9/L (baseline = 1.0 × 10^9/L ), platelet improvement: increase from baseline ≥ 30 × 10^9/L (baseline = 100 × 10^9/L)
Time Frame	Baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

Number of patients who met criteria varied across parameters

Arm/Group Title	Erythropoietin Alpha	Deferasirox + Erythropoietin Alpha
Arm/Group Description	Starting dose was erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were switched to the combination arm. At any time when erythroid response was achieved, erythropoietin treatment was stopped until end of study.	Starting dose was deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, erythropoietin dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were discontinued from the study. At any time when erythroid response was achieved, erythropoietin treatment was stopped study and Deferasirox treatment was continued until end of study
Measure Participants	12	11
Platelets	58.7 (23.93)	66.3 (22.74)
Neutrophils	1.2 (1.16)	2.4 (1.57)

6. Secondary Outcome

Title	Summary of Erythroid Response in Participants Randomized to EPO Alone at Baseline and Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set)
Description	Erythroid response: hemoglobin increase from baseline > = 1.5 g/dL (baseline <11 g/dL)
Time Frame	Week 13 up to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EPO+DFX (12 Weeks)
Arm/Group Description	Patients randomized to EPO alone with inadequate response at 12 weeks who had been switched over to combination EPO+DFX
Measure Participants	5
Number [participants]	0 0%

7. Secondary Outcome

Title	Summary of Erythroid Response Within 24 Weeks in Participants Randomized to EPO at Baseline and Not Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set)
Description	Erythroid response: hemoglobin increase from baseline > = 1.5 g/dL (baseline <11 g/dL). Percentages are based on N. Confidence intervals are calculated using Clopper-Pearson method. Hemoglobin value is at time of first response
Time Frame	baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EPO (24 Weeks)
Arm/Group Description	Patients who were in EPO alone group and were not switched to EPO+DFX after 12 weeks,
Measure Participants	7
Number (95% Confidence Interval) [percentage of participants]	71.4 595%

8. Secondary Outcome

Title	Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set)
Description	Absolute change in serum ferritin from baseline
Time Frame	Baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

Number of patients analyzed varied by visit

Arm/Group Title	Erythropoietin Alpha
Arm/Group Description	Starting dose was erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were switched to the combination arm. At any time when erythroid response was achieved, erythropoietin treatment was stopped until end of study.
Measure Participants	7
Responders - Week 5	-98.5
Responders - Week 9	-79.0
Responders - Week 13	24.8
Responders - Week 17	-57.8
Responders - Week 21	-39.8
Non-responders - Week 5	-352
Non-responders - Week 9	-189
Non-responders - Week 13	-44.5

9. Secondary Outcome

Title	Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set)
Description	Absolute change in serum ferritin from baseline
Time Frame	Baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

Number of patients analyzed varied by visit

Arm/Group Title	Deferasirox + Erythropoietin Alpha
Arm/Group Description	Starting dose was deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, erythropoietin dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were discontinued from the study. At any time when erythroid response was achieved, erythropoietin treatment was stopped study and Deferasirox treatment was continued until end of study
Measure Participants	11
Responders - Week 5	-82.5
Responders - Week 9	-139
Responders - Week 13|	-121
Responders - Week 17	16.5
Responders - Week 21	-95.5
Non-responders - Week 5	-38.0
Non-responders - Week 9|	-144
Non-responders - Week 13|	-155
Non-responders - Week 17	-123
Non-responders - Week 21	-291

10. Secondary Outcome

Title	Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set)
Description	Absolute change in serum ferritin from baseline
Time Frame	Baseline up 24 weeks

Outcome Measure Data

Analysis Population Description

Number of patients analyzed varied by visit

Arm/Group Title	EPO+DFX at 12
Arm/Group Description	Patients randomized to EPO alone with inadequate response at 12 weeks who had been switched over to combination EPO+DFX
Measure Participants	5
Responders - Week 5	-116
Responders - Week 9	-136
Responders - Week 13	59.5
Responders - Week 17	74.5
Non-responders - Week 5	-68.3
Non-responders - Week 9	-148
Non-responders - Week 13	220.4
Non-responders - Week 17	-16.6
Non-responders - Week 21	-10.5

11. Secondary Outcome

Title	Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set)
Description	This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy.
Time Frame	Baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

Number of patients analyzed varied by visit

Arm/Group Title	Erythropoietin Alpha
Arm/Group Description	Starting dose was erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were switched to the combination arm. At any time when erythroid response was achieved, erythropoietin treatment was stopped until end of study.
Measure Participants	7
Responders - Week 5	1.5
Responders - Week 9	1.9
Responders - Week 13	1.7
Responders - Week 17	1.6
Responders - Week 21	0.8
Non-responders - Week 5	-0.9
Non-responders - Week 9	-1.7
Non-responders - Week 13	-2.5

12. Secondary Outcome

Title	Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set)
Description	This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy.
Time Frame	Baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

Number of patients analyzed varied by visit

Arm/Group Title	Deferasirox + Erythropoietin Alpha
Arm/Group Description	Starting dose was deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, erythropoietin dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were discontinued from the study. At any time when erythroid response was achieved, erythropoietin treatment was stopped study and Deferasirox treatment was continued until end of study
Measure Participants	11
Responders - Week 5	0.7
Responders - Week 9	1.6
Responders - Week 13	2.9
Responders - Week 17	2.4
Responders - Week 21	1.7
Non-responders - Week 5	-0.1
Non-responders - Week 9	0.0
Non-responders - Week 13	0.2
Non-responders - Week 17	-0.5
Non-responders - Week 21	-0.6

13. Secondary Outcome

Title	Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set)
Description	This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy. The time-course of Hb and its absolute changes from baseline was summarized by descriptive statistics by visit and erythroid response. Patients randomized to EPO and not switching after 12 weeks to EPO+DFX would consist of only responders.
Time Frame	Baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

Number of patients analyzed varied by visit

Arm/Group Title	EPO+DFX at 12 Weeks
Arm/Group Description	This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy. The time-course of Hb and its absolute changes from baseline was summarized by descriptive statistics by visit and erythroid response. Patients randomized to EPO and not switching after 12 weeks to EPO+DFX would consist of only responders
Measure Participants	5
Responders - Week 5	1.2
Responders - Week 9|	1.8
Responders - Week 13|	0.7
Responders - Week 17|	-0.6
Non-responders - Week 5	0.3
Non-responders - Week 9|	0.5
Non-responders - Week 13	0.4
Non-responders - Week 17|	0.0
Non-responders - Week 21	0.0

Adverse Events

Time Frame	Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 24 weeks
Adverse Event Reporting Description	There was no washout period during the study before switch of treatment. Therefore effects (including AEs) from long lasting treatment like EPO can potentially still be observed after the switch, e.g. from EPO+DFX to DFX alone. Thus the resulting includes both treatments (DFX-EPO category). The same applies for staring EPO alone and switching to EPO plus DFX.
Arm/Group Title	EPO A		EPO+DFX DT		EPO+DFX FCT		Switched to DFX+EPO After 12 Weeks
Arm/Group Description	Patients receiving EPO during the first 12 weeks and no switching to EPO+DFX arm		Patients receiving EPO+DFX from week 1 and continuing with EPO+DFX after 12 weeks or with DFX alone after 12 weeks		Patients receiving EPO alone and switched to EPO+DFX after 12 weeks of treatment		Switched to DFX+EPO after 12 weeks
All Cause Mortality
	EPO A		EPO+DFX DT		EPO+DFX FCT		Switched to DFX+EPO After 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/10 (0%)		0/1 (0%)		0/5 (0%)
Serious Adverse Events
	EPO A		EPO+DFX DT		EPO+DFX FCT		Switched to DFX+EPO After 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		1/10 (10%)		1/1 (100%)		1/5 (20%)
Cardiac disorders
Tachycardia	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Gastrointestinal disorders
Inguinal hernia	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
General disorders
Pyrexia	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		0/5 (0%)
Infections and infestations
Diverticulitis	0/7 (0%)		0/10 (0%)		1/1 (100%)		0/5 (0%)
Injury, poisoning and procedural complications
Femoral neck fracture	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Investigations
C-reactive protein increased	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		0/5 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Back pain	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		0/5 (0%)
Musculoskeletal pain	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		0/5 (0%)
Nervous system disorders
Syncope	0/7 (0%)		0/10 (0%)		1/1 (100%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	EPO A		EPO+DFX DT		EPO+DFX FCT		Switched to DFX+EPO After 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/7 (57.1%)		10/10 (100%)		1/1 (100%)		5/5 (100%)
Blood and lymphatic system disorders
Anaemia	2/7 (28.6%)		2/10 (20%)		0/1 (0%)		1/5 (20%)
Ear and labyrinth disorders
Vertigo	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Gastrointestinal disorders
Abdominal pain upper	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Anal fissure	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		0/5 (0%)
Constipation	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Diarrhoea	0/7 (0%)		3/10 (30%)		1/1 (100%)		0/5 (0%)
Gastrooesophageal reflux disease	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Inguinal hernia	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Toothache	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
General disorders
Asthenia	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Gravitational oedema	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Injection site bruising	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Oedema peripheral	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Pyrexia	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Hepatobiliary disorders
Hepatic function abnormal	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Infections and infestations
Conjunctivitis	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Gastroenteritis	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Herpes zoster	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		0/5 (0%)
Hordeolum	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Influenza	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		0/5 (0%)
Localised infection	0/7 (0%)		0/10 (0%)		0/1 (0%)		2/5 (40%)
Lung infection	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Sinusitis	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Upper respiratory tract infection	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Investigations
Alanine aminotransferase increased	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Aspartate aminotransferase increased	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Blood creatinine increased	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Blood uric acid increased	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Haemoglobin decreased	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Heart rate increased	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Weight decreased	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		0/5 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Back pain	1/7 (14.3%)		1/10 (10%)		0/1 (0%)		1/5 (20%)
Neck pain	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Pain in extremity	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		0/5 (0%)
Renal and urinary disorders
Renal impairment	0/7 (0%)		1/10 (10%)		0/1 (0%)		1/5 (20%)
Respiratory, thoracic and mediastinal disorders
Cough	0/7 (0%)		1/10 (10%)		0/1 (0%)		0/5 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/7 (0%)		0/10 (0%)		0/1 (0%)		1/5 (20%)
Rash	0/7 (0%)		1/10 (10%)		0/1 (0%)		1/5 (20%)
Rash maculo-papular	1/7 (14.3%)		0/10 (0%)		0/1 (0%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.