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

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT00438841

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

4.3

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: bortezomib Drug: cyclophosphamide Drug: dexamethasone Drug: thalidomide	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

43 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2006

Anticipated Primary Completion Date :

Dec 1, 2008

Outcome Measures

Primary Outcome Measures

Response rate []

Secondary Outcome Measures

Safety and tolerability []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California	United States	94704
2	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
3	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California	United States	92262
4	Sutter Cancer Center	Sacramento	California	United States	95816
5	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus	Boca Raton	Florida	United States	33486
6	St. Vincent's Comprehensive Cancer Center - Manhattan	New York	New York	United States	10011
7	Oregon Health and Science University Cancer Institute	Portland	Oregon	United States	97239
8	Lone Star Oncology - Austin	Austin	Texas	United States	78759
9	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109-1023
10	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024