Deferasirox in Treating Patients With Very Low, Low, or Intermediate-Risk Red Blood Cell Transfusion Dependent Anemia or Myelodysplastic Syndrome

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Terminated
CT.gov ID
NCT02943668
Collaborator
National Cancer Institute (NCI) (NIH), Novartis Pharmaceuticals (Industry)
2
Enrollment
1
Location
1
Arm
21.5
Actual Duration (Months)
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial studies how well deferasirox works in treating patients with very low, low, or intermediate-risk anemia or myelodysplastic syndrome that depends on red blood cell transfusions. Deferasirox may treat too much iron in the blood caused by blood transfusions.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess the activity of iron chelation therapy (ICT) with deferasirox, in patients with anemia due to myelodysplastic syndrome (MDS).
SECONDARY OBJECTIVES:
  1. Reduction in red blood cell (RBC) transfusion requirements. II. Hematologic improvement.

  2. Change in serum ferritin levels from baseline to the end of the study as measured on a monthly basis.

  3. Safety and tolerability of deferasirox.

EXPLORATORY OBJECTIVES:
  1. Blood and marrow samples will be taken to study erythropoiesis and the impact of iron overload on erythropoiesis.

OUTLINE: Patients receive deferasirox orally (PO) once daily (QD). Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Study Design

Study Type:
Interventional
Actual Enrollment :
2 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Deferasirox in Patients With Myelodysplastic Syndromes Who Are Anemic With Iron Overload
Actual Study Start Date :
Mar 2, 2017
Actual Primary Completion Date :
Dec 17, 2018
Actual Study Completion Date :
Dec 17, 2018

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment (deferasirox)

Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Deferasirox
Given PO
Other Names:
  • Exjade
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of Patients That Achieve Erythroid Hematologic Improvement. [At 6 months]

      As defined by the modified International Working Group (IWG) response criteria: Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation. Platelet response (pretreatment, < 100 x 10^9/L) Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100% Neutrophil response (pretreatment, < 1.0 x 10^9/L) 1) At least 100% increase and an absolute increase > 0.5 x 10^9/L

    Secondary Outcome Measures

    1. Change in Red Blood Cell (RBC) Transfusion Requirements [Baseline up to 12 months]

      Assessed monthly for up to twelve months.

    2. Change in Serum Ferritin Levels [Baseline up to 12 months]

      Assessed monthly for up to twelve months.

    3. Proportion of Patients Who Achieve Granulocyte or Platelet Hematologic Improvement [At 6 months]

      As defined by the modified International Working Group (IWG) response criteria: Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation. Platelet response (pretreatment, < 100 x 10^9/L) Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100% Neutrophil response (pretreatment, < 1.0 x 10^9/L) 1) At least 100% increase and an absolute increase > 0.5 x 10^9/L

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Capable of giving written informed consent prior to any study-specific procedures

    • Diagnosis of MDS as defined by the World Health Organization (WHO) diagnostic criteria

    • Have very low, low or intermediate-risk disease by the Revised International Prognostic Scoring System (IPSS-R)

    • Baseline serum ferritin level >= 100 ng/mL

    • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

    • Anemia defined as: hemoglobin =< 10.0 g/dL

    • Bilirubin =< 1.5 times upper limit of normal (ULN)

    • Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =< 3.5 times ULN

    • Serum creatinine =< 1.5 x ULN

    • Estimated glomerular filtration rate (GFR) > 40 mL/min

    • Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of deferasirox

    • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment; effective contraception methods include:

    • Placement of an intrauterine device (IUD) or intrauterine system (IUS)

    • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

    • Total abstinence or (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception

    • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment

    • Male sterilization (at least 6 months prior to screening); for female subjects on the study, the vasectomized male partner should be the sole partner for that subject

    • Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential; sexually active males must use a condom during intercourse while taking drug and for 28 days after stopping study medication and should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid

    • Females with childbearing potential* must have had a negative urine or serum pregnancy test =< 7 days before the first dose of deferasirox and must also not be breastfeeding

    • Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

    Exclusion Criteria:
    • If the patient is currently receiving erythroid stimulating agents (ESA) with plans to continue during study, less than 2 months duration of ESA prior to starting study drug and no dose escalation within 2 months of start of study drug

    • If the patient is being treated with granulocyte-colony stimulating factor (GCSF) and/or a TPO-mimetic (for example, eltrombopag or romiplostim) with plans to continue during the study: Less than 2 months duration of GCSF or the TPO-mimetic treatment prior to starting study drug; or GCSF and/or TPO-mimetic has been added to ESA therapy within 2 months of start of study drug

    • If patient is being treated with lenalidomide with plans to continue during the study: Stable dose for less than 3 months prior to start of study drug

    • If patient is being treated with hypomethylating agents (HMA) (for example, azacitidine or decitabine) with plans to continue during the study: Stable dose for less than 6 months prior to start of study drug

    • Currently enrolled in, or discontinued within the last 14 days from a clinical trial involving an investigational product or non-approved use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

    • Presence of >= 10% blast by morphologic examination of bone marrow aspirate or biopsy

    • Platelets =< 50,000

    • Microcytosis on screening blood cell count (CBC) (mean corpuscular volume [MCV] < 81 fL)

    • Active gastrointestinal (GI) ulceration or hemorrhage

    • Have a serious preexisting medical condition that, in the opinion of the investigator would preclude participation in the study (for example a GI disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndrome) or that would result in a life expectancy of less than 1 year

    • Known hypersensitivity to deferasirox

    • History of non-transfusional hemosiderosis

    • Prior hematopoietic stem cell transplant for the diagnosis of MDS

    • A second primary malignancy that in the judgment of the principal investigator (PI) or designee may affect the interpretation of results

    • Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis

    • Currently using aluminum-containing antacid products

    • History of clinically significant auditory or ocular toxicity with ICT

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Fred Hutch/University of Washington Cancer ConsortiumSeattleWashingtonUnited States98109

    Sponsors and Collaborators

    • Fred Hutchinson Cancer Center
    • National Cancer Institute (NCI)
    • Novartis Pharmaceuticals

    Investigators

    • Principal Investigator: Bart Scott, Fred Hutch/University of Washington Cancer Consortium

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02943668
    Other Study ID Numbers:
    • 9422
    • NCI-2016-01457
    • 9422
    • P30CA015704
    First Posted:
    Oct 25, 2016
    Last Update Posted:
    Jul 1, 2020
    Last Verified:
    Apr 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleTreatment (Deferasirox)
    Arm/Group DescriptionPatients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
    Period Title: Overall Study
    STARTED2
    COMPLETED1
    NOT COMPLETED1

    Baseline Characteristics

    Arm/Group TitleTreatment (Deferasirox)
    Arm/Group DescriptionPatients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
    Overall Participants2
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    0
    0%
    >=65 years
    2
    100%
    Sex: Female, Male (Count of Participants)
    Female
    1
    50%
    Male
    1
    50%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    2
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    2
    100%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    2
    100%

    Outcome Measures

    1. Primary Outcome
    TitleProportion of Patients That Achieve Erythroid Hematologic Improvement.
    DescriptionAs defined by the modified International Working Group (IWG) response criteria: Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation. Platelet response (pretreatment, < 100 x 10^9/L) Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100% Neutrophil response (pretreatment, < 1.0 x 10^9/L) 1) At least 100% increase and an absolute increase > 0.5 x 10^9/L
    Time FrameAt 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment (Deferasirox)
    Arm/Group DescriptionPatients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies Of the two participants on the study, none achieved erythroid hematologic improvement as defined by the modified IWG response criteria at 6 months.
    Measure Participants2
    Count of Participants [Participants]
    0
    0%
    2. Secondary Outcome
    TitleChange in Red Blood Cell (RBC) Transfusion Requirements
    DescriptionAssessed monthly for up to twelve months.
    Time FrameBaseline up to 12 months

    Outcome Measure Data

    Analysis Population Description
    Data for the 2 participants is presented as 2 different groups to show the individual RBC transfusion requirements per month, at each point in time
    Arm/Group TitlePatient 1Patient 2
    Arm/Group DescriptionPatients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studiesPatients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
    Measure Participants11
    Transfusion requirement at Baseline
    4
    1
    Transfusion requirement at time off-treatment
    2
    2
    3. Secondary Outcome
    TitleChange in Serum Ferritin Levels
    DescriptionAssessed monthly for up to twelve months.
    Time FrameBaseline up to 12 months

    Outcome Measure Data

    Analysis Population Description
    Data for the 2 participants is presented as 2 different groups to show the individual serum ferritin levels at each point in time
    Arm/Group TitlePatient 1Patient 2
    Arm/Group DescriptionPatients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studiesPatients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
    Measure Participants11
    Baseline
    6025
    755
    1 month
    6637
    778
    2 months
    6010
    827
    3 months
    6405
    583
    4 months
    22360
    414
    5 months
    7252
    652
    6 months
    5697
    776
    7 months
    4832
    880
    8 months
    4054
    NA
    9 months
    3933
    NA
    10 months
    3728
    NA
    11 months
    NA
    NA
    12 months
    NA
    NA
    4. Secondary Outcome
    TitleProportion of Patients Who Achieve Granulocyte or Platelet Hematologic Improvement
    DescriptionAs defined by the modified International Working Group (IWG) response criteria: Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation. Platelet response (pretreatment, < 100 x 10^9/L) Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100% Neutrophil response (pretreatment, < 1.0 x 10^9/L) 1) At least 100% increase and an absolute increase > 0.5 x 10^9/L
    Time FrameAt 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment (Deferasirox)
    Arm/Group DescriptionPatients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
    Measure Participants2
    Count of Participants [Participants]
    1
    50%

    Adverse Events

    Time FrameEnrollment through 30 days after the last administration of the study treatment
    Adverse Event Reporting Description
    Arm/Group TitleTreatment (Deferasirox)
    Arm/Group DescriptionPatients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
    All Cause Mortality
    Treatment (Deferasirox)
    Affected / at Risk (%)# Events
    Total1/2 (50%)
    Serious Adverse Events
    Treatment (Deferasirox)
    Affected / at Risk (%)# Events
    Total1/2 (50%)
    Gastrointestinal disorders
    Constipation1/2 (50%)
    Other (Not Including Serious) Adverse Events
    Treatment (Deferasirox)
    Affected / at Risk (%)# Events
    Total1/2 (50%)
    Blood and lymphatic system disorders
    Anemia- due to acute blood loss1/2 (50%)
    Cardiac disorders
    A-fib w/ rapid ventricular rate1/2 (50%)
    Gastrointestinal disorders
    Hemorrhoids1/2 (50%)
    Constipation1/2 (50%)
    Infections and infestations
    Clostrid Difficile1/2 (50%)
    Sinus Infection1/2 (50%)
    Urinary tract infection1/2 (50%)
    Injury, poisoning and procedural complications
    Fracture- Lft. Lateral Tibia Plateau1/2 (50%)
    Fall1/2 (50%)
    Fracture- Lft. Second Metatarsal1/2 (50%)
    Fracture- Lft. Wrist1/2 (50%)
    Investigations
    Weight loss1/2 (50%)
    Alanine Amniotransferase- increased1/2 (50%)
    Asparate Aminotransferase increased1/2 (50%)
    Psychiatric disorders
    Insomnia1/2 (50%)
    Renal and urinary disorders
    Elevated Creatine/ urine protein1/2 (50%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea1/2 (50%)

    Limitations/Caveats

    [Not Specified]

    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. Bart Scott
    OrganizationFred Hutch Cancer Research Center
    Phone206.667.1990
    Emailbscott@fredhutch.org
    Responsible Party:
    Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02943668
    Other Study ID Numbers:
    • 9422
    • NCI-2016-01457
    • 9422
    • P30CA015704
    First Posted:
    Oct 25, 2016
    Last Update Posted:
    Jul 1, 2020
    Last Verified:
    Apr 1, 2020