Bortezomib in Treating Patients With Myelodysplastic Syndromes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jane Liesveld, University of Rochester
ClinicalTrials.gov Identifier:
NCT00262873
First received: December 6, 2005
Last updated: April 4, 2016
Last verified: April 2016
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndromes
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Pilot Study of VELCADE in Patients With MDS

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Number of Participants Who Experienced an Adverse Event [ Time Frame: For 21 days/course for up to 12 courses ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Experienced Cytopenias [ Time Frame: 21 Days/course for up to 12 courses ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Interleukin 6 Levels in Serum [ Time Frame: day 14 ] [ Designated as safety issue: No ]

    interleukin-6 levels were measured by enzyme-linked immunosorbant assay ELISA in serum from participants exposed to bortezomib.

    Levels were measured at Day 0 and Day 14 of cycle 1 of the clinical trial.


  • Vascular Endothelial Growth Factor (VEGF) Levels in Serum [ Time Frame: day 14 ] [ Designated as safety issue: No ]
    VEGF levels were measured by ELISA (R&DSystems) in serum from participants exposed to bortezomib. Levels were measured at Day 0 and Day 14 of cycle 1 of the clinical trial.

  • Average Percentage of Light Density Cells in Apoptosis [ Time Frame: day 14 ] [ Designated as safety issue: No ]
    The CD34+ fraction of light density marrow obtained from patients at baseline and while receiving bortezomib were assessed through measurement of Annexin V (assay obtained form R&D Systems) and by flow cytometry analysis.

  • Average Number of Colony Forming Unit-granulocyte-macrophages in Bone Marrow [ Time Frame: day 14 ] [ Designated as safety issue: No ]
    Colony forming unit-granulocyte-macrophage (CFU-GM) progenitors, erythroid burst forming units (BFU-E), and leukemia colony forming units (CFU-L) were measured at day 0 and day 14 of cycle 1. Five × 10(4) light density cell for granulocyte-macrophage colony forming unit (CFU-GM) or erythroid burst forming unit (BFU-E) assays were plated in 0.9% methylcellulose, 30% FCS, 2 mmol/L L-glutamine, 10−4 mol/L β-mercaptoethanol, and 1% BSA with 3U/ml human erythropoietin, 10 ng/ml GM-CSF, 10 ng/ml IL-3, and 50 ng/ml stem cell factor (SCF) (c-kit ligand). For leukemia colony forming units (CFU-Ls), the plating mixture was comparable with the exception that the cytokines utilized were 4 U/ml erythropoietin, 10 ng/ml GM-CSF, 10 ng/ml IL-3, 100 ng/ml c-kit ligand, and 100 ng/ml Flt3 ligand. The methylcellulose mixture and associated reagents were purchased from Stem Cell Technologies (Vancouver, BC). Colonies were scored at Day 14 and were defined as > 20 grouped cells.

  • Average Number of Erthroid Burst Forming Units in Bone Marrow [ Time Frame: day 14 ] [ Designated as safety issue: No ]
    Colony forming unit-granulocyte-macrophage (CFU-GM) progenitors, erythroid burst forming units (BFU-E), and leukemia colony forming units (CFU-L) were measured at day 0 and day 14 of cycle 1. Five × 10(4) light density cell for granulocyte-macrophage colony forming unit (CFU-GM) or erythroid burst forming unit (BFU-E) assays were plated in 0.9% methylcellulose, 30% FCS, 2 mmol/L L-glutamine, 10−4 mol/L β-mercaptoethanol, and 1% BSA with 3U/ml human erythropoietin, 10 ng/ml GM-CSF, 10 ng/ml IL-3, and 50 ng/ml stem cell factor (SCF) (c-kit ligand). For leukemia colony forming units (CFU-Ls), the plating mixture was comparable with the exception that the cytokines utilized were 4 U/ml erythropoietin, 10 ng/ml GM-CSF, 10 ng/ml IL-3, 100 ng/ml c-kit ligand, and 100 ng/ml Flt3 ligand. The methylcellulose mixture and associated reagents were purchased from Stem Cell Technologies (Vancouver, BC). Colonies were scored at Day 14 and were defined as > 20 grouped cells.

  • Average Number of Leukemia Forming Units in Bone Marrow [ Time Frame: day 14 ] [ Designated as safety issue: No ]
    Colony forming unit-granulocyte-macrophage (CFU-GM) progenitors, erythroid burst forming units (BFU-E), and leukemia colony forming units (CFU-L) were measured at day 0 and day 14 of cycle 1. Five × 10(4) light density cell for granulocyte-macrophage colony forming unit (CFU-GM) or erythroid burst forming unit (BFU-E) assays were plated in 0.9% methylcellulose, 30% FCS, 2 mmol/L L-glutamine, 10−4 mol/L β-mercaptoethanol, and 1% BSA with 3U/ml human erythropoietin, 10 ng/ml GM-CSF, 10 ng/ml IL-3, and 50 ng/ml stem cell factor (SCF) (c-kit ligand). For leukemia colony forming units (CFU-Ls), the plating mixture was comparable with the exception that the cytokines utilized were 4 U/ml erythropoietin, 10 ng/ml GM-CSF, 10 ng/ml IL-3, 100 ng/ml c-kit ligand, and 100 ng/ml Flt3 ligand. The methylcellulose mixture and associated reagents were purchased from Stem Cell Technologies (Vancouver, BC). Colonies were scored at Day 14 and were defined as > 20 grouped cells.


Enrollment: 8
Study Start Date: May 2005
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib Drug: bortezomib

Detailed Description:

OBJECTIVES:

Primary

  • Determine the efficacy of bortezomib, in terms of reduced cytopenia, in patients with myelodysplastic syndromes.
  • Determine the safety and toxic effects of this drug in these patients.

Secondary

  • Determine changes in marrow blast percentage or karyotypic profile in patients treated with this drug.

OUTLINE: This is an open-label study.

Patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00262873

Locations
United States, New York
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
Investigators
Study Chair: Jane L. Liesveld, MD James P. Wilmot Cancer Center
  More Information

Publications:
Responsible Party: Jane Liesveld, attending physician, University of Rochester
ClinicalTrials.gov Identifier: NCT00262873     History of Changes
Other Study ID Numbers: CDR0000449689  URCC-U20403  MILLENNIUM-i34103-042 
Study First Received: December 6, 2005
Results First Received: February 29, 2016
Last Updated: April 4, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Rochester:
previously treated myelodysplastic syndromes
refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
refractory anemia
secondary myelodysplastic syndromes
de novo myelodysplastic syndromes

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
Bortezomib
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2016