Study of Velcade and Thalidomide in Patients With Myelodysplasia

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

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.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: bortezomib

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 Type: Interventional
• Enrollment: 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
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.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Dana-Farber Cancer Institute; Beth Israel Deaconess Medical Center; Brigham and Women's Hospital
• Investigators: Principal Investigator: Karen Ballen, M, Massachusetts General Hospital, Harvard University

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Study Completion: April 1, 2007

Study Registration Dates

• First Submitted: December 30, 2005
• First Submitted That Met QC Criteria: December 30, 2005
• First Posted (Estimate): January 4, 2006

Study Record Updates

• Last Update Posted (Estimate): March 13, 2008
• Last Update Submitted That Met QC Criteria: March 7, 2008
• Last Verified: March 1, 2008

More Information

Terms related to this study

• Keywords: Thalidomide; MDS; Bortezomib; Velcade; Myelodysplastic syndrome; Myelodysplasia
• Additional Relevant MeSH Terms: Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Preleukemia; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: 04-381