Phase II Study to Evaluate Overall Response in Patients With Higher Risk Myelodysplastic Syndromes (MDS) Treated With Azacitidine With or Without Deferasirox.
Condition: High Risk MDS
MeSH terms: Preleukemia; Myelodysplastic Syndromes
Intervention: Azacitidine; Azacitidine plus Deferasirox
Intervention description: SC or IV AZA at 75mg/m2 7 days/28 day cycle; SC or IV AZA at 75mg/m2 7 days/28 day cycle DFX 10mg/kg/day
Intervention MeSH terms: Azacitidine; Deferasirox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Int-2 MDS

Summary:

      The primary objective of the study is to compare the overall response rate (inclusive of
      complete response, partial response and hematologic improvement) per IWG 2006 criteria in
      patients with higher risk MDS treated with azacitidine with or without deferasirox achieved
      over the course of one year. Hematologic improvement must be maintained for at least 8 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

        Male or Female, age ≥ 18 years Patients with higher risk MDS with a blast count < 20% at
        the time of screening IPSS Int-2 or High Risk Serum Ferritin ≥ 300 ng/mL at screening.

        Sexually active women must use an effective method of contraception, or must have undergone
        clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be
        postmenopausal (defined as amenorrhea for at least 12 months)

        Exclusion Criteria:

        Patients currently receiving any therapy other than AZA for MDS (a ≥ 4 week washout period
        for any agent (excluding AZA) used to treat MDS prior to first dose of study treatment is
        required).

        Patients who have received > 2 cycles of AZA or decitabine at the time of randomization.
        Patients who have received iron chelation therapy within 1 month of screening.

        Patients who have received growth factors within 1 month of screening. Patients who have
        received Revlimid within 1 month of screening. Patients who have undergone hematopoietic
        stem cell transplant. ECOG Performance Status > 2 Systemic diseases (cardiovascular, renal,
        hepatic, etc.) which would prevent study treatment Patients with uncontrolled systemic
        hypertension Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or
        unstable cardiac or coronary artery disease not controlled by standard medical therapy
        Patients with a diagnosis of or history of clinically relevant ocular toxicity related to
        iron chelation Diagnosis of liver cirrhosis (either established diagnosis or diagnosis by
        liver biopsy or central ultrasound reading) Clinical or laboratory evidence of active
        Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA
        positive and ALT above the normal range). History of HIV positive test result (ELISA or
        Western blot) Presence of a surgical or medical condition which might significantly alter
        the absorption, distribution, metabolism or excretion of study drug Patients with an active
        malignancy (currently or within the past two years) with the exception of basal cell skin
        carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in
        situ. History of drug or alcohol abuse within the 12 months prior to enrollment. History of
        non-compliance to medical regimens or patients who are considered potentially unreliable
        and/or not cooperative.

        Patients with a known hypersensitivity to azacitidine, mannitol, or deferasirox. Calculated
        creatinine clearance <40mL/min Serum creatinine greater than 1.5x ULN at screening Urine
        protein/creatinine ratio> 1 AST or ALT greater than 3x ULN at screening Direct Bilirubin
        greater than 1.5x ULN at screening. Patients who received treatment with systemic
        investigational drug within the past 4 weeks or topical investigational drug within the
        past 7 days or are planning to receive other investigational drugs while participating in
        the study Patients participating in another therapeutic clinical trial Pregnant or nursing
        (lactating) women, where pregnancy is defined as the state of a female after conception and
        until the termination of gestation, confirmed by a positive hCG laboratory test. 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.
        Sexually active males unless they use a condom during intercourse while taking drug and for
        3 months after stopping AZA and should not father a child in this period.