Study of Velcade and Thalidomide in Patients With Myelodysplasia

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT00271804

Collaborator

Dana-Farber Cancer Institute (Other), Brigham and Women's Hospital (Other), Beth Israel Deaconess Medical Center (Other)

Enrollment

Locations

Duration (Months)

9.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome	Drug: bortezomib	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2005

Study Completion Date :

Apr 1, 2007

Outcome Measures

Primary Outcome Measures

The primary objective is to establish the maximally tolerated dose of bortezomib that can be administered with thalidomide in patient with myelodysplasia. []

Secondary Outcome Measures

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. []
Determine the toxicity profile of bortezomib when used in combination with thalidomide for patients with myelodysplasia. []
Determine the relationship between NF-kB expression and clinical response to bortezomib and thalidomide. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115