Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies

Sponsor
Wake Forest University Health Sciences (Other)
Overall Status
Completed
CT.gov ID
NCT01273766
Collaborator
National Cancer Institute (NCI) (NIH)
16
Enrollment
1
Location
3
Arms
47
Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Deferasirox may remove excess iron from the body caused by blood transfusions.

PURPOSE: This clinical trial studies deferasirox in treating iron overload caused by blood transfusions in patients with hematologic malignancies.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: deferasirox
  • Other: laboratory biomarker analysis
  • Other: enzyme-linked immunosorbent assay
Phase 2

Detailed Description

PRIMARY OBJECTIVES: I. To determine the effects of the iron-chelating agent deferasirox on changes in: neutrophil function; macrophage function; lymphocyte function.

SECONDARY OBJECTIVES: I. To determine the effect of chelation on the incidence of bacterial, viral and fungal infections documented by clinical, microbiologically-proven versus radiologically-proven criteria. II. To determine the effect of iron chelation on mortality and morbidity with incidence of the following parameters: Need for hospitalization; Duration of hospitalization; Need for ventilatory support; Need for exchange transfusion/apheresis; Need for treatment with antifungals or antibiotics for documented infections.

OUTLINE: Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity.

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Supportive Care
Official Title:
Impact of Intervention With Deferasirox on the Immune Function of Patients With Hematologic Diseases and Transfusion-Related Iron Overload
Study Start Date :
Jan 1, 2011
Actual Primary Completion Date :
Mar 1, 2012
Actual Study Completion Date :
Dec 1, 2014

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm I

Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity.

Drug: deferasirox
Given orally
Other Names:
  • Exjade
  • ICL670
  • Other: laboratory biomarker analysis
    Correlative studies

    Other: enzyme-linked immunosorbent assay
    Correlative studies
    Other Names:
  • ELISA
  • No Intervention: control arm

    blood tested on healthy patients

    No Intervention: correlative

    treated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis

    Outcome Measures

    Primary Outcome Measures

    1. Changes in Mean Neutrophil Values (as Measured by Lab) for Arm 1 (Other Arms Were Used for Calibration Only) [Baseline, up to 6 months]

      Changes in Neutrophils between baseline and mean neutrophils values during treatment (measured after each dose)

    Secondary Outcome Measures

    1. Need for Hospitalization, Ventilator Support, Exchange Transfusion/Apheresis or Treatment With Antifungals or Antibiotics [Baseline, up to 6 months]

      Records will be assessed at baseline and prospectively while on study.

    2. Cumulative Incidence of Documented Bacterial, Fungal, and Viral Infections [Baseline, up to 6 months]

      Records will be assessed at baseline and prospectively while on study.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must have a pathology confirmed diagnosis of one of the following: myelodysplastic syndrome (MDS); acute leukemia; multiple myeloma; myelofibrosis; lymphoma; chronic anemia; sickle cell anemia

    • Iron score >= 2

    • Absolute Neutrophil Count (ANC) >= 1,000

    • Platelets >= 50,000

    • Albumin >= 2 g/dL

    • Alkaline phosphatase =< 5X Upper Limit of Normal (ULN)

    • Total bilirubin =< 1.5

    • Creatinine =< 2X age-appropriate Upper Limit of Normal (ULN) OR creatinine clearance

    = 40 ml/min

    • Serum Glutamic Oxaloacetic Transaminase (SGOT) [AST] and Serum Glutamic Pyruvic Transaminase (SGPT) [ALT] =< 5X Upper Limit of Normal (ULN)

    • Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1

    • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

    • Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:
    • Patients with active disease undergoing chemotherapy treatment

    • Patient who have been treated with rituximab or immunomodulating drugs =< 1 month prior to enrollment

    • HIV-positive patients

    • Hepatitis-C positive patients

    • Women who are pregnant or breastfeeding

    • Patients on hemodialysis/patients with renal failure

    • Patients with sepsis or acute illness

    • Known hypersensitivity to deferasirox

    • Patients with moderate or severe hearing loss as defined by audiogram

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Comprehensive Cancer Center of Wake Forest UniversityWinston-SalemNorth CarolinaUnited States27157

    Sponsors and Collaborators

    • Wake Forest University Health Sciences
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Mary Ann Knovich, MD, Wake Forest University Health Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Wake Forest University Health Sciences
    ClinicalTrials.gov Identifier:
    NCT01273766
    Other Study ID Numbers:
    • IRB00015287
    • NCI-2010-02228
    • CCCWFU 97710
    First Posted:
    Jan 10, 2011
    Last Update Posted:
    Sep 7, 2018
    Last Verified:
    Aug 1, 2018

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleArm IControl ArmCorrelative
    Arm/Group DescriptionPatients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studiesblood tested on healthy patientstreated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis
    Period Title: Overall Study
    STARTED475
    COMPLETED475
    NOT COMPLETED000

    Baseline Characteristics

    Arm/Group TitleArm IControl ArmCorrelativeTotal
    Arm/Group DescriptionPatients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studiesblood tested on healthy patientstreated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysisTotal of all reporting groups
    Overall Participants47516
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    75%
    7
    100%
    4
    80%
    14
    87.5%
    >=65 years
    1
    25%
    0
    0%
    1
    20%
    2
    12.5%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    53.1
    (12.9)
    40.1
    (7.0)
    55.0
    (17.6)
    48.0
    (14.5)
    Sex: Female, Male (Count of Participants)
    Female
    2
    50%
    6
    85.7%
    1
    20%
    9
    56.3%
    Male
    2
    50%
    1
    14.3%
    4
    80%
    7
    43.8%
    Region of Enrollment (participants) [Number]
    United States
    4
    100%
    7
    100%
    5
    100%
    16
    100%

    Outcome Measures

    1. Primary Outcome
    TitleChanges in Mean Neutrophil Values (as Measured by Lab) for Arm 1 (Other Arms Were Used for Calibration Only)
    DescriptionChanges in Neutrophils between baseline and mean neutrophils values during treatment (measured after each dose)
    Time FrameBaseline, up to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm I
    Arm/Group DescriptionPatients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studies
    Measure Participants4
    Mean (Standard Deviation) [10^9 Neutrophils per Liter]
    7.8
    (138.4)
    2. Secondary Outcome
    TitleNeed for Hospitalization, Ventilator Support, Exchange Transfusion/Apheresis or Treatment With Antifungals or Antibiotics
    DescriptionRecords will be assessed at baseline and prospectively while on study.
    Time FrameBaseline, up to 6 months

    Outcome Measure Data

    Analysis Population Description
    Number analyzed in rows differs from overall because data was not collected on all participants.
    Arm/Group TitleArm ICorrelative
    Arm/Group DescriptionPatients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studiestreated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis
    Measure Participants45
    Baseline : Hospitalization
    2
    50%
    5
    71.4%
    Baseline : Ventilator
    0
    0%
    1
    14.3%
    Baseline : Transfusion
    0
    0%
    0
    0%
    Baseline : Antibiotics
    0
    0%
    5
    71.4%
    1 Month : Hospitalization
    1
    25%
    1
    14.3%
    1 Month : Ventilator
    0
    0%
    0
    0%
    1 Month : Transfusion
    0
    0%
    1
    14.3%
    1 Month : Antibiotics
    1
    25%
    1
    14.3%
    2 Month : Hospitalization
    0
    0%
    1
    14.3%
    2 Month : Ventilator
    0
    0%
    0
    0%
    2 Month : Transfusion
    0
    0%
    1
    14.3%
    2 Month : Antibiotics
    0
    0%
    1
    14.3%
    3 Month : Hospitalization
    0
    0%
    1
    14.3%
    3 Month : Ventilator
    0
    0%
    0
    0%
    3 Month : Transfusion
    0
    0%
    1
    14.3%
    3 Month : Antibiotics
    0
    0%
    0
    0%
    4 Month : Hospitalization
    0
    0%
    1
    14.3%
    4 Month : Ventilator
    0
    0%
    1
    14.3%
    4 Month : Transfusion
    0
    0%
    1
    14.3%
    4 Month : Antibiotics
    1
    25%
    1
    14.3%
    5 Month : Hospitalization
    0
    0%
    2
    28.6%
    5 Month : Ventilator
    0
    0%
    0
    0%
    5 Month : Transfusion
    0
    0%
    0
    0%
    5 Month : Antibiotics
    0
    0%
    1
    14.3%
    6 Month : Hospitalization
    3
    75%
    0
    0%
    6 Month : Ventilator
    0
    0%
    0
    0%
    6 Month : Transfusion
    0
    0%
    0
    0%
    6 Month : Antibiotics
    1
    25%
    0
    0%
    3. Secondary Outcome
    TitleCumulative Incidence of Documented Bacterial, Fungal, and Viral Infections
    DescriptionRecords will be assessed at baseline and prospectively while on study.
    Time FrameBaseline, up to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm ICorrelative
    Arm/Group DescriptionPatients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studiestreated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis
    Measure Participants45
    Count of Participants [Participants]
    2
    50%
    5
    71.4%

    Adverse Events

    Time Frame6 months
    Adverse Event Reporting Description only patients on Arm I (recieving drug on protocol) were tracked for toxicities
    Arm/Group TitleArm IControl ArmCorrelative
    Arm/Group DescriptionPatients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. deferasirox : Given orally laboratory biomarker analysis : Correlative studies enzyme-linked immunosorbent assay : Correlative studiesblood tested on healthy patientstreated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis
    All Cause Mortality
    Arm IControl ArmCorrelative
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Arm IControl ArmCorrelative
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total4/4 (100%) 0/0 (NaN) 0/0 (NaN)
    General disorders
    Fatigue2/4 (50%) 30/0 (NaN) 00/0 (NaN) 0
    Heartburn/dyspepsia1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Confusion1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    "Distension bloating, abdominal"1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Infections and infestations
    Infection Bladder1/4 (25%) 20/0 (NaN) 00/0 (NaN) 0
    Cystitis1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Lung infection1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Infection Sinus1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Injury, poisoning and procedural complications
    Infection with normal ANC or Grade 1 or 2 neutrophils: Nose1/4 (25%) 20/0 (NaN) 00/0 (NaN) 0
    Investigations
    hyperglycemia2/4 (50%) 60/0 (NaN) 00/0 (NaN) 0
    hyponatremia1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    hypokalemia1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    serum glutamic pyruvic transaminase1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Lipase1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Lymphopenia1/4 (25%) 20/0 (NaN) 00/0 (NaN) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnea2/4 (50%) 20/0 (NaN) 00/0 (NaN) 0
    Vascular disorders
    Thrombosis/thrombus/embolism1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Other (Not Including Serious) Adverse Events
    Arm IControl ArmCorrelative
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total4/4 (100%) 0/0 (NaN) 0/0 (NaN)
    Eye disorders
    Ocular/Visual - Other1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Dry eye syndrome1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    blurred vision1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Gastrointestinal disorders
    Nausea1/4 (25%) 20/0 (NaN) 00/0 (NaN) 0
    Vomiting1/4 (25%) 30/0 (NaN) 00/0 (NaN) 0
    Constipation2/4 (50%) 40/0 (NaN) 00/0 (NaN) 0
    General disorders
    Anorexia2/4 (50%) 20/0 (NaN) 00/0 (NaN) 0
    Gastrointestinal - Other1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Taste alteration1/4 (25%) 50/0 (NaN) 00/0 (NaN) 0
    Insomnia1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Fatigue1/4 (25%) 20/0 (NaN) 00/0 (NaN) 0
    Weight loss1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Pain: Head/headache1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Urinary frequency/urgency1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Renal/Genitourinary - Other1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Intra-operative Injury1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Musculoskeletal Soft Tissue - Other1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Dry mouth3/4 (75%) 30/0 (NaN) 00/0 (NaN) 0
    Dehydration2/4 (50%) 30/0 (NaN) 00/0 (NaN) 0
    Pruritus/itching1/4 (25%) 20/0 (NaN) 00/0 (NaN) 0
    Pain: Abdomen1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Ataxia1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Obstruction Bladder1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Pain Bladder1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Urine color change1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Anal Incontinence1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Memory impairment1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Pain: Muscle1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Pain Oral cavity1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Pain: Extremity-limb1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Hyperpigmentation1/4 (25%) 50/0 (NaN) 00/0 (NaN) 0
    Infections and infestations
    Lung infection2/4 (50%) 30/0 (NaN) 00/0 (NaN) 0
    Mucositis/stomatitis Oral cavity2/4 (50%) 20/0 (NaN) 00/0 (NaN) 0
    Mucositis/stomatitis Oral cavity3/4 (75%) 110/0 (NaN) 00/0 (NaN) 0
    Infection Lip perioral1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Blood Infection with high grade neutropenia1/4 (25%) 20/0 (NaN) 00/0 (NaN) 0
    Investigations
    Low WBC1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    low Platelets3/4 (75%) 90/0 (NaN) 00/0 (NaN) 0
    Low Hemoglobin4/4 (100%) 150/0 (NaN) 00/0 (NaN) 0
    Alkaline phosphatase3/4 (75%) 100/0 (NaN) 00/0 (NaN) 0
    Creatinine2/4 (50%) 70/0 (NaN) 00/0 (NaN) 0
    Proteinuria2/4 (50%) 20/0 (NaN) 00/0 (NaN) 0
    hyperglycemia4/4 (100%) 150/0 (NaN) 00/0 (NaN) 0
    hypoglycemia1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    hypocalcemia4/4 (100%) 40/0 (NaN) 00/0 (NaN) 0
    hypomagnesemia3/4 (75%) 30/0 (NaN) 00/0 (NaN) 0
    hyponatremia3/4 (75%) 70/0 (NaN) 00/0 (NaN) 0
    hypokalemia1/4 (25%) 30/0 (NaN) 00/0 (NaN) 0
    hypoalbuminemia4/4 (100%) 60/0 (NaN) 00/0 (NaN) 0
    hyperbilirubinemia1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    serum glutamic pyruvic transaminase2/4 (50%) 100/0 (NaN) 00/0 (NaN) 0
    serum glutamic oxaloacetic transaminase1/4 (25%) 60/0 (NaN) 00/0 (NaN) 0
    hypermagnesemia2/4 (50%) 40/0 (NaN) 00/0 (NaN) 0
    hyperkalemia1/4 (25%) 20/0 (NaN) 00/0 (NaN) 0
    Amylase1/4 (25%) 20/0 (NaN) 00/0 (NaN) 0
    gamma-Glutamyl transpeptidase1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Glomerular filtration rate2/4 (50%) 40/0 (NaN) 00/0 (NaN) 0
    Lipase1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Lymphopenia2/4 (50%) 40/0 (NaN) 00/0 (NaN) 0
    Nervous system disorders
    Tremor1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnea1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Cough2/4 (50%) 30/0 (NaN) 00/0 (NaN) 0
    Bronchospasm wheezing1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Skin and subcutaneous tissue disorders
    Dermatology/Skin1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Rash/desquamation2/4 (50%) 50/0 (NaN) 00/0 (NaN) 0
    Allergic rhinitis1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0
    Vascular disorders
    Hemorrhage GU: Urinary1/4 (25%) 20/0 (NaN) 00/0 (NaN) 0
    Thrombosis/embolism (vascular access-related)1/4 (25%) 10/0 (NaN) 00/0 (NaN) 0

    Limitations/Caveats

    adverse events were only tracked on Arm I

    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.

    Results Point of Contact

    Name/TitleDr. Mary Ann Knovich
    OrganizationComprehensive Cancer Center of Wake Forest University
    Phone336-716-7973
    Emailmknovich@wakehealth.edu
    Responsible Party:
    Wake Forest University Health Sciences
    ClinicalTrials.gov Identifier:
    NCT01273766
    Other Study ID Numbers:
    • IRB00015287
    • NCI-2010-02228
    • CCCWFU 97710
    First Posted:
    Jan 10, 2011
    Last Update Posted:
    Sep 7, 2018
    Last Verified:
    Aug 1, 2018