Study of Velcade and Thalidomide in Patients With Myelodysplasia

Myelodysplastic Syndrome Clinical Trial

Official title:

Phase I Dose Escalation Trial of Bortezomib in Combination With Thalidomide in Patients With Myelodysplasia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00271804
• Other study ID #: 04-381
• Status: Terminated
• Phase: Phase 1
• First received: December 30, 2005
• Last updated: March 7, 2008
• Start date: June 2005
• Est. completion date: April 2007

Study information

• Verified date: March 2008
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out what the maximal tolerated dose of Velcade can be given with thalidomide in patients with myelodysplasia.

Description:

Initial studies using Velcade in myelodysplasia with early results demonstrating that 35% had a partial response and 25% had stable disease. The combination of Velcade and thalidomide has been studied in patients with multiple myeloma, but not in patients with myelodysplasia. The CRR in the MM patients was 22%, with a good safety profile.

This is a phase 1, prospective, open-label, dose escalation study to evaluate the DLT and MTD of velcade with given in combination with thalidomide in patients with myelodysplasia. Treatment will be given as an outpatient. Patients will receive 4 days of Velcade (days 1, 4, 8, 11) and 21 days of thalidomide 50 mg/day for each 21 day cycle. There will be 3 cohorts of 3-6 patients each, plus 10 additional patients. The tree dose levels ill be 0.7, 1.0 and 1.3 mg/m2. Patients may continue to be treated up to 6 cycles. Cycles 2-6 will start within 2 weeks of completion of the previous cycle. Disease response will be evaluated after cycle 3 and 6.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Myelodysplastic syndrome with a IPSS score of 0.5 or greater

• May have had prior chemo/radiotherapy for another malignancy or myelodysplasia

• ECOG performance status of 0-2

• Life expectancy greater than 3 months

• Total bilirubin </+ 2xULN

• ALT and AST </+ 3xULN

• Calculated creatinine clearance > 30 ml/min

• Use of appropriate method of contraception during the study

• ANC > 0.5 x 10(9)

• Platelet count > 30 x 10(9)

• Consideration of treatment with 5 azacytidine is encouraged by not required

Exclusion Criteria:

• Ejection fraction < 40%

• myocardial infarction within 6 months of enrollment of New York Heart Association Class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities

• Women who are pregnant or breast-feeding

• Major surgery within 4 weeks prior to enrollment

• >/= grade 2 peripheral neuropathy within 14 days prior to enrollment

• Uncontrolled intercurrent illness

• Serious medical or psychiatric illness that could potentially interfere with the completion of treatment

• Hypersensitivity to bortezomib, boron, or mannitol

• Received an investigational drug within 14 days of enrollment

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• bortezomib

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective is to establish the maximally tolerated dose of bortezomib that can be administered with thalidomide in patient with myelodysplasia.
Secondary	Assess efficacy in terms of the number of patients attaining a 50% reduction in blast percentage, or 50% reduction in number of red blood cell and/or platelet transfusions.
Secondary	Determine the toxicity profile of bortezomib when used in combination with thalidomide for patients with myelodysplasia.
Secondary	Determine the relationship between NF-kB expression and clinical response to bortezomib and thalidomide.