Exjade-Early-Trial

• Sponsor: University of Erlangen-Nürnberg Medical School (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01058369
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 33.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Study outline: Deferasirox (Exjade®) is regularly used in severe iron overload in order to avoid organ damage of liver, heart and other organs. It has been proposed, that iron overload may not only impose damage to other organs but also to the bone marrow and thus worsen hematopoietic insufficiency in patients with MDS. Patients presenting with low or INT-1 risk MDS with only mild iron overload will be treated with deferasirox in this study. It will be analyzed if hematological improvement can be observed during this treatment.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: Deferasirox (Novartis Pharma)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Early Treatment With Deferasirox (Exjade®) in Low Risk MDS - a Prospective Multicentre Single-arm Single-stage Phase II Study -
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Deferasirox	Drug: Deferasirox (Novartis Pharma); Treatment period 102 weeks. Starting dose 10mg/kg/day. Up to 30/mg/kg according to dose adjustment table as specified in the protocol; Other Names: Exjade(R)

Outcome Measures

Primary Outcome Measures

1. Fraction of Patients With Hematologic Improvement According to Modified IWG Criteria (Reduction of Transfusions and/or Increase in Hb, Improvement of Neutropenia and Thrombocytopenia) [within two years]

Secondary Outcome Measures

1. Evaluate the Safety and Tolerability Profile of Deferasirox in MDS Patients [within two years]

2. Effectiveness of Iron Depletion [within two years]

3. Correlation Between Hematological Improvement and Effectiveness of Iron Depletion [two years]

4. Development of Bone Marrow Morphology [two years]

5. Correlation Between Hematological Improvement and Pretreatment Parameters. Extension of This Analysis to MDS Patients on Deferasirox Within the Licensed Indication (More Severe Iron Overload) [two years]

6. Overall Survival [within two years]

7. AML-free Survival [within two years]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• MDS of subtype RA, RARS, RCMD, RCMD-RS (i.e. lower risk)

• RAEB I allowed, if clinically stable for > 3 months

• 5q-minus syndrome allowed, if lenalidomide unsuccessful or unavailable at the time of inclusion

• IPSS score < intermediate-1

• transfusion dependent or Hb < 10,5 g/dl

• History of less than 20 units of red blood cell transfusions or 100mL/kg of prepacked red blood cells (PRBCs), except for transfusions for acute bleeding

• Serum ferritin > 300 µg/l and < 1500 μg/l. This level should have been verified at least at two occasions within 3 months. Samples must be obtained in the absence of concomitant severe infection

• no indication for EPO (due to high endogenous EPO levels) or EPO without benefit in the past

• no indication and/or no plans for cytostatic drugs

• no previous exposure to cytostatic drugs, thalidomide, lenalidomide, G-CSF or EPO or exposure to any of these drugs has been terminated since > 8 weeks (4 weeks for G-CSF).

• no indication and/or no plans for stem cell transplantation

• stable or worsening cytopenia during the past 8 weeks. If in doubt, extend screening period to >= 8 weeks

• Patients of either gender and age > 18 years

• Life expectancy > 12 months

• Females of childbearing potential must use double-barrier contraception (for example orale contraception and condom).

• Mental ability of the patient to understand explications concerning the study and to understand and follow instructions of the investigating physician

• Written informed consent by the patient

Exclusion Criteria:

• Treatment with deferasirox or other chelation therapy for periods > 4 weeks before study start

• Patients with intolerance to Deferasirox

• Patients with a concomitant second malignant disease, possibly interfering with life expectancy

• Patients with mean levels of alanine aminotransferase (ALT) > 5x ULN

• Patients with uncontrolled systemic hypertension

• Patients with serum creatinine > 1.5x the upper limit of normal (ULN) or a creatinine clearance < 60 ml/min according to the MDRD formula (Levey 2005)

• History of nephrotic syndrome

• Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the patient from undergoing study treatment

• Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment

• Patients treated with systemic investigational drugs within the past 4 weeks or topical investigational drug within the past 7 days

• Any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following:

• history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;

• history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;

• history of pancreatic injury or pancreatitis; indications of impaired pancreatic function/injury as indicated by abnormal lipase or amylase;

• history of urinary obstruction or difficulty in voiding

• History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative

• History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by laboratory assays conducted during the screening period

• Patients with active uncontrolled infectious disease

• Pregnancy or breast feeding

• QT > 470 msec on screening ECG

• Patients with a history of Torsades de Pointes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medizinische Klinik 5, Universitätsklinikum Erlangen	Erlangen	Bavaria	Germany	91054

Sponsors and Collaborators

• University of Erlangen-Nürnberg Medical School
• Novartis Pharmaceuticals

Investigators

• Study Chair: Stefan Krause, Prof. Dr., Medizinische Klinik 5, Universitätsklinikum Erlangen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Erlangen-Nürnberg Medical School
• ClinicalTrials.gov Identifier: NCT01058369
• Other Study ID Numbers: CICL670ADE06T
• First Posted: Jan 28, 2010
• Last Update Posted: Oct 6, 2020
• Last Verified: Sep 1, 2020

• Additional relevant MeSH terms: Myelodysplastic Syndromes; Deferasirox

Study Results

Participant Flow

Arm/Group Title	Deferasirox
Arm/Group Description	Deferasirox (Novartis Pharma): Treatment period 102 weeks. Starting dose 10mg/kg/day. Up to 30/mg/kg according to dose adjustment table as specified in the protocol
Period Title: Overall Study
STARTED	2
COMPLETED	0
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Deferasirox
Arm/Group Description	Deferasirox (Novartis Pharma): Treatment period 102 weeks. Starting dose 10mg/kg/day. Up to 30/mg/kg according to dose adjustment table as specified in the protocol
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	42.5
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Region of Enrollment (participants) [Number]
Germany	2 100%

Outcome Measures

1. Primary Outcome

Title	Fraction of Patients With Hematologic Improvement According to Modified IWG Criteria (Reduction of Transfusions and/or Increase in Hb, Improvement of Neutropenia and Thrombocytopenia)
Time Frame	within two years

Outcome Measure Data

Analysis Population Description

Trial prematurely ended due to insufficient recruitment before Primary endpoint was reached by any subject

Arm/Group Title	Deferasirox
Arm/Group Description	Deferasirox (Novartis Pharma): Treatment period 102 weeks. Starting dose 10mg/kg/day. Up to 30/mg/kg according to dose adjustment table as specified in the protocol
Measure Participants	0

2. Secondary Outcome

Title	Evaluate the Safety and Tolerability Profile of Deferasirox in MDS Patients
Time Frame	within two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Effectiveness of Iron Depletion
Time Frame	within two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Correlation Between Hematological Improvement and Effectiveness of Iron Depletion
Time Frame	two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Development of Bone Marrow Morphology
Time Frame	two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Correlation Between Hematological Improvement and Pretreatment Parameters. Extension of This Analysis to MDS Patients on Deferasirox Within the Licensed Indication (More Severe Iron Overload)
Time Frame	two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Overall Survival
Time Frame	within two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	AML-free Survival
Time Frame	within two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Deferasirox
Arm/Group Description	Deferasirox (Novartis Pharma): Treatment period 102 weeks. Starting dose 10mg/kg/day. Up to 30/mg/kg according to dose adjustment table as specified in the protocol
All Cause Mortality
	Deferasirox
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Deferasirox
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Blood and lymphatic system disorders
acute myeloid leukaemia	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/2 (50%)	1
Other (Not Including Serious) Adverse Events
	Deferasirox
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Gastrointestinal disorders
nausea	1/2 (50%)	1
dyspepsia	1/2 (50%)	1
abdominal pain upper	1/2 (50%)	1
General disorders
fatigue	2/2 (100%)	2
Injury, poisoning and procedural complications
wound	1/2 (50%)	1
Musculoskeletal and connective tissue disorders
back pain	1/2 (50%)	1
pain in extremity	1/2 (50%)	1
Psychiatric disorders
depression	1/2 (50%)	1
emotional distress	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
dyspnea	1/2 (50%)	1
Skin and subcutaneous tissue disorders
petechiae	1/2 (50%)	1
Vascular disorders
haematoma	1/2 (50%)	1
thrombophlebitis	1/2 (50%)	1
hypertension	1/2 (50%)	1
gingival bleeding	1/2 (50%)	1

Limitations/Caveats

Early Termination leading to small numbers of subjects enrolled; number of subjects analysed = 0

More Information

Certain Agreements

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

There IS 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.