Exjade-Early-Trial

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

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 DiseaseIntervention/TreatmentPhase
  • 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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1Medizinische Klinik 5, Universitätsklinikum ErlangenErlangenBavariaGermany91054

    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:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionDeferasirox (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
    STARTED2
    COMPLETED0
    NOT COMPLETED2

    Baseline Characteristics

    Arm/Group TitleDeferasirox
    Arm/Group DescriptionDeferasirox (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 Participants2
    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
    TitleFraction of Patients With Hematologic Improvement According to Modified IWG Criteria (Reduction of Transfusions and/or Increase in Hb, Improvement of Neutropenia and Thrombocytopenia)
    Description
    Time Framewithin 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 TitleDeferasirox
    Arm/Group DescriptionDeferasirox (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 Participants0
    2. Secondary Outcome
    TitleEvaluate the Safety and Tolerability Profile of Deferasirox in MDS Patients
    Description
    Time Framewithin two years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    TitleEffectiveness of Iron Depletion
    Description
    Time Framewithin two years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    TitleCorrelation Between Hematological Improvement and Effectiveness of Iron Depletion
    Description
    Time Frametwo years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    TitleDevelopment of Bone Marrow Morphology
    Description
    Time Frametwo years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Secondary Outcome
    TitleCorrelation Between Hematological Improvement and Pretreatment Parameters. Extension of This Analysis to MDS Patients on Deferasirox Within the Licensed Indication (More Severe Iron Overload)
    Description
    Time Frametwo years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Secondary Outcome
    TitleOverall Survival
    Description
    Time Framewithin two years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Secondary Outcome
    TitleAML-free Survival
    Description
    Time Framewithin two years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionDeferasirox (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
    Total1/2 (50%)
    Blood and lymphatic system disorders
    acute myeloid leukaemia1/2 (50%) 1
    Respiratory, thoracic and mediastinal disorders
    Pneumonia1/2 (50%) 1
    Other (Not Including Serious) Adverse Events
    Deferasirox
    Affected / at Risk (%)# Events
    Total2/2 (100%)
    Gastrointestinal disorders
    nausea1/2 (50%) 1
    dyspepsia1/2 (50%) 1
    abdominal pain upper1/2 (50%) 1
    General disorders
    fatigue2/2 (100%) 2
    Injury, poisoning and procedural complications
    wound1/2 (50%) 1
    Musculoskeletal and connective tissue disorders
    back pain1/2 (50%) 1
    pain in extremity1/2 (50%) 1
    Psychiatric disorders
    depression1/2 (50%) 1
    emotional distress1/2 (50%) 1
    Respiratory, thoracic and mediastinal disorders
    dyspnea1/2 (50%) 1
    Skin and subcutaneous tissue disorders
    petechiae1/2 (50%) 1
    Vascular disorders
    haematoma1/2 (50%) 1
    thrombophlebitis1/2 (50%) 1
    hypertension1/2 (50%) 1
    gingival bleeding1/2 (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.

    Results Point of Contact

    Name/TitleProf. Dr. med. Stefan Krause
    OrganizationUniversitätsklinikum Erlangen, Medizinische Klinik 5
    Phone
    Emailstefan.krause@uk-erlangen.de
    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