Bortezomib, Cyclophosphamide, Dexamethasone, and Thalidomide in Treating Patients With Newly Diagnosed, Previously Untreated Multiple Myeloma

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

Official title:

A Phase II Trial With VELCADE® (PS-341), Cytoxan (Cyclophosphamide), Dexamethasone and Thalomid® (VEL-CTD) in Previously Untreated Multiple Myeloma Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00438841
• Other study ID #: CDR0000536219
• Secondary ID: FHCRC-2123.00
• Status: Active, not recruiting
• Phase: Phase 2
• First received: February 20, 2007
• Last updated: March 12, 2009
• Start date: August 2006

Study information

• Verified date: March 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• 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. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving bortezomib together with cyclophosphamide, dexamethasone, and thalidomide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with cyclophosphamide, dexamethasone, and thalidomide works in treating patients with newly diagnosed, previously untreated multiple myeloma.

Description:

OBJECTIVES:

Primary

• Determine the response rate in patients with newly diagnosed, previously untreated multiple myeloma treated with bortezomib, cyclophosphamide, dexamethasone, and thalidomide.

Secondary

• Determine the safety and tolerability of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive bortezomib IV on days 1, 4, 8, and 11; cyclophosphamide IV on days 1 and 8 of courses 1-3; oral thalidomide once daily on days 1-21 beginning in course 4; and dexamethasone IV or orally once daily on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 43
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma meeting 1 of the following criteria:

• Monoclonal immunoglobulin spike on serum electrophoresis (IgG > 3.5 g/dL or IgA > 2.0 g/dL) and kappa or lambda light chain excretion > 1 g/day by 24-hour urine protein electrophoresis AND meets any of the following criteria:

• Bone marrow plasmacytosis (10-30% plasma cells)

• Lytic bone lesions

• Monoclonal immunoglobulin of lesser magnitude present and bone marrow plasmacytosis (10-30% plasma cells) AND meets any of the following criteria:

• Lytic bone lesions

• IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL

• Bone marrow plasmacytosis (> 30% plasma cells) or plasmacytoma on tissue biopsy AND meets any of the following criteria:

• Monoclonal immunoglobulin of lesser magnitude present

• Lytic bone lesions

• IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL

• FreeLite testing abnormal and kappa:lambda light chain ratio abnormal

• Symptomatic disease requiring treatment

• Documented related organ or tissue involvement, if present

• Measurable disease, defined as 1 of the following:

• Monoclonal immunoglobulin spike on serum electrophoresis = 1 g/dL and/or urine monoclonal immunoglobulin spike = 200 mg/day

• Abnormal FreeLite testing (for nonsecretors)

• Patients with nonsecretory disease must meet either of the following criteria for measurability:

• Has measurable protein by FreeLite testing

• Untreated soft tissue plasmacytoma and/or evaluable disease in bone marrow

• Newly diagnosed, previously untreated disease

• No POEMS syndrome (i.e., plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes)

• No plasma cell leukemia

PATIENT CHARACTERISTICS:

• Karnofsky performance status 50-100%

• Platelet count = 100,000/mm³ (= 50,000/mm³ if bone marrow is extensively infiltrated)

• Extensive infiltration is defined as > 50% myeloma cells or plasma cells

• Hemoglobin = 8.5 g/dL

• Absolute neutrophil count = 1,500/mm³

• AST and ALT = 2 times upper limit of normal (ULN)

• Bilirubin = 1.5 times ULN (unless clearly related to the disease)

• Creatinine clearance = 20 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use 2 methods of effective contraception = 4 weeks prior to beginning treatment, during, and for = 4 weeks after completion of study treatment

• No impaired kidney function requiring dialysis

• No uncontrolled infection

• No HIV positivity

• No known active hepatitis B or C

• No cardiovascular disease including, but not limited to, any of the following:

• Myocardial infarction within the past 6 months

• New York Heart Association class II-IV heart failure

• Uncontrolled angina

• Severe uncontrolled ventricular arrhythmias

• Clinically significant pericardial disease

• Acute ischemic or active conduction system abnormalities by EKG

• No history of allergic reactions to compounds containing mannitol, bortezomib, or cyclophosphamide

• No second malignancy requiring concurrent treatment

• No other serious medical or psychiatric illness that would preclude study compliance

• No peripheral neuropathy = grade 1

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, immunotherapy, vaccine therapy, therapeutic doses of steroids, or other agents for the treatment of active myeloma

• Drugs given to prevent onset of myeloma allowed

• Bisphosphonates for hypercalcemia or short course corticosteroids for hypercalcemia or cord compromise allowed

• Prior local radiotherapy with or without a brief exposure to steroids allowed

• More than 4 weeks since prior and no concurrent radiotherapy

• Spot radiotherapy to = 3 vertebrae allowed

• No concurrent steroids at > 10 mg of prednisone daily (or the equivalent) for other medical conditions (e.g., asthma, systemic lupus erythematosus, or rheumatoid arthritis)

• No other concurrent chemotherapy or investigational agents

• Concurrent daily acetylsalicylic acid required during course 4-6 of study treatment

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Drug:
• bortezomib

• cyclophosphamide

• dexamethasone

• thalidomide

Locations

Country	Name	City	State
United States	Lone Star Oncology - Austin	Austin	Texas
United States	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California
United States	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus	Boca Raton	Florida
United States	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California
United States	St. Vincent's Comprehensive Cancer Center - Manhattan	New York	New York
United States	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California
United States	Oregon Health and Science University Cancer Institute	Portland	Oregon
United States	Sutter Cancer Center	Sacramento	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate			No
Secondary	Safety and tolerability			Yes