Bortezomib in Treating Patients With Myelodysplastic Syndromes

Myelodysplastic Syndromes Clinical Trial

Official title:

A Phase II Pilot Study of VELCADE in Patients With MDS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00262873
• Other study ID #: CDR0000449689
• Secondary ID: URCC-U20403MILLE
• Status: Completed
• Phase: Phase 2
• First received: December 6, 2005
• Last updated: September 16, 2014
• Start date: May 2005
• Est. completion date: October 2010

Study information

• Verified date: September 2014
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Data Safety Monitoring Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• bortezomib

Locations

Country	Name	City	State
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
University of Rochester

Country where clinical trial is conducted

United States, 

References & 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/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as measured by NCI toxicity criteria after every course		For 21 days/course for up to 12 courses	Yes
Primary	Efficacy as measured by improvement of cytopenias based on complete blood counts after every course		21 Days/course for up to 12 courses	No
Secondary	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		21 Days/course for up to 12 courses	No