Clinical trial NCT00262873: Bortezomib in Treating Patients With Myelodysplastic Syndromes
Official title: A Phase II Pilot Study of VELCADE in Patients With MDS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2005-12-07
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Number of Participants Who Experienced an Adverse Event
timeFrame: For 21 days/course for up to 12 courses
measure: Number of Participants Who Experienced Cytopenias
timeFrame: 21 Days/course for up to 12 courses
Secondary outcomes:
measure: Interleukin 6 Levels in Serum
timeFrame: day 14
measure: Vascular Endothelial Growth Factor (VEGF) Levels in Serum
timeFrame: day 14
measure: Average Percentage of Light Density Cells in Apoptosis
timeFrame: day 14
measure: Average Number of Colony Forming Unit-granulocyte-macrophages in Bone Marrow
timeFrame: day 14
measure: Average Number of Erthroid Burst Forming Units in Bone Marrow
timeFrame: day 14
measure: Average Number of Leukemia Forming Units in Bone Marrow
timeFrame: day 14
Other outcomes:
Locations:
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
Study officials:
affiliation: James P. Wilmot Cancer Center
name: Jane L. Liesveld, MD
role: STUDY_CHAIR
References:
citation: 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.