Bortezomib in Treating Patients With Myelodysplastic Syndromes
Condition: Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: bortezomib
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: previously treated myelodysplastic syndromes; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory anemia; secondary myelodysplastic syndromes; de novo myelodysplastic syndromes

Summary:

      RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth.

      PURPOSE: This phase II trial is studying how well bortezomib works in treating patients with
      myelodysplastic syndromes.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of myelodysplastic syndromes (MDS)

          -  Requires treatment or transfusion support for MDS, as indicated by 1 of the following:

               -  Demonstrates transfusion or epoetin alfa dependence

                    -  Transfusion dependence is defined as requiring ≥ 2 units of packed RBCs
                       within an 8-week period prior to study entry

               -  Hemoglobin < 11g/dL on 2 separate occasions 2 weeks apart

                    -  No iron, cyanocobalamin (vitamin B_12), or folic acid deficiency or other
                       causes of anemia

          -  Must have 1 of the following FAB subtypes:

               -  Refractory anemia

               -  Refractory anemia with ringed sideroblasts

               -  Refractory anemia with excess blasts

               -  Secondary MDS (if ≥ 3 years since active primary cancer)

          -  No chronic myelomonocytic leukemia

          -  Not refractory to platelet transfusion support (i.e., inability to maintain platelet
             count > 20,000/mm^3 with transfusion)

          -  No current acute myelogenous leukemia (e.g., > 30% blasts)

        PATIENT CHARACTERISTICS:

        Performance status

          -  Karnofsky 50-100%

        Life expectancy

          -  At least 6 months

        Hematopoietic

          -  See Disease Characteristics

        Hepatic

          -  Bilirubin ≤ 2 mg/dL

          -  AST and ALT < 2 times upper limit of normal

        Renal

          -  Creatinine clearance ≥ 30 mL/min

        Cardiovascular

          -  No significant cardiovascular condition that would preclude study participation

          -  No uncontrolled hypertension

        Pulmonary

          -  No significant pulmonary condition that would preclude study participation

        Immunologic

          -  No serious concurrent infection

               -  Active infections must be adequately treated with antibiotics prior to study
                  entry

          -  No hypersensitivity to bortezomib, boron, or mannitol

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for up to 4 weeks after
             completion of study treatment

          -  No peripheral neuropathy ≥ grade 2

          -  No uncontrolled seizure activity, as defined by no activity within the past year on
             stable anticonvulsant medications

          -  No other malignancy within the past 3 years except adequately treated basal cell skin
             cancer or carcinoma in situ of the cervix

          -  No endocrine, neurologic, or other systemic disease that would preclude study entry

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  See Disease Characteristics

          -  No prior allogeneic bone marrow transplantation

          -  Concurrent transfusion support allowed

          -  Concurrent epoetin alfa or darbepoetin alfa allowed if initiated before start of study
             therapy, dose is stable for ≥ 4 weeks, and dose is stable during study participation

          -  No concurrent platelet growth factor support

          -  No concurrent thalidomide

        Chemotherapy

          -  No concurrent chemotherapy

          -  No concurrent hydroxyurea

        Endocrine therapy

          -  Concurrent corticosteroids for chronic autoimmune or inflammatory condition allowed if
             initiated before start of study therapy and maintained on a stable or decreasing dose

        Other

          -  Recovered from all prior therapies

          -  At least 4 weeks since prior MDS therapy, except epoetin alfa, darbepoetin alfa,
             filgrastim (G-CSF), pegfilgrastim (G-CSF), or transfusion support

          -  At least 30 days since prior investigational agents

          -  No prior bortezomib

          -  No other concurrent investigational agents

          -  No other concurrent therapy for MDS