Bortezomib in Treating Patients With Myelodysplastic Syndromes

NCT00262873 | Completed Phase 2 Results DMC

• 3 other identifiers: CDR0000449689URCC-U20403MILLENNIUM-i34103-042
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myelodysplastic Syndromes

Keywords

previously treated myelodysplastic syndromes; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory anemia; secondary myelodysplastic syndromes; de novo myelodysplastic syndromes

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced an Adverse Event

  For 21 days/course for up to 12 courses

• Number of Participants Who Experienced Cytopenias

  21 Days/course for up to 12 courses

Secondary Outcomes (6)

• Interleukin 6 Levels in Serum

  day 14

• Vascular Endothelial Growth Factor (VEGF) Levels in Serum

  day 14

• Average Percentage of Light Density Cells in Apoptosis

  day 14

• Average Number of Colony Forming Unit-granulocyte-macrophages in Bone Marrow

  day 14

• Average Number of Erthroid Burst Forming Units in Bone Marrow

  day 14

Study Arms (1)

Bortezomib

EXPERIMENTAL

Drug: bortezomib

Interventions

bortezomib DRUG

Bortezomib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Related Publications (1)

• Liesveld JL, Rosell KE, Bechelli J, Lu C, Messina P, Mulford D, Ifthikharuddin JJ, Jordan CT, Phillips Ii GL. Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines. Cancer Invest. 2011 Aug;29(7):439-50. doi: 10.3109/07357907.2011.590567.

  PMID: 21740082 RESULT

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Anemia, Refractory

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

All study visits were completed and the trial concluded normally for the limited number of enrolled participants; therefore, the study was considered to have been completed. However, the study is under-powered.

Results Point of Contact

• Title: Jane Liesveld, M.D.
• Organization: University of Rochester

Jane_Liesveld@urmc.rochester.edu

585-275-4099

Study Officials

• Jane L. Liesveld, MD

  James P. Wilmot Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: attending physician

Study Record Dates

• First Submitted: December 6, 2005
• First Posted: December 7, 2005
• Study Start: May 1, 2005
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: May 9, 2016
• Results First Posted: May 9, 2016

Record last verified: 2016-04

Locations

US (1)