Bortezomib in Treating Patients With Myelodysplastic Syndromes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Rochester
ClinicalTrials.gov Identifier:
NCT00262873
First received: December 6, 2005
Last updated: December 12, 2013
Last verified: December 2013
  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:
  • Safety as measured by NCI toxicity criteria after every course [ Time Frame: For 21 days/course for up to 12 courses ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by improvement of cytopenias based on complete blood counts after every course [ Time Frame: 21 Days/course for up to 12 courses ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Marrow and karyotype response and in vitro correlates (apoptosis, proliferation, etc.) assessed with marrow aspirate and biopsy sampling at baseline, day 14, and after courses 3, 6, and 12 [ Time Frame: 21 Days/course for up to 12 courses ] [ Designated as safety issue: No ]

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
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

Additional Information:
Publications:
Responsible Party: 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
Last Updated: December 12, 2013
Health Authority: United States: Data Safety Monitoring Board

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
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014