Bortezomib, Dexamethasone, and Cyclophosphamide in Treating Older Patients With Multiple Myeloma

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies the side effects and how well lower doses of bortezomib, dexamethasone, and cyclophosphamide work in treating older patients with multiple myeloma. 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. Giving cyclophosphamide daily may kill more cancer cells. Giving bortezomib, cyclophosphamide, and dexamethasone may be an effective treatment for multiple myeloma.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) and toxicity rate of therapy with weekly bortezomib combined with oral metronomic cyclophosphamide and low-dose dexamethasone. SECONDARY OBJECTIVES: I. To determine overall survival. II. To describe the association between disease status, treatment response, treatment toxicity, quality of life, functional status, risk for development of frailty, and inflammatory cytokine levels. OUTLINE: Patients receive bortezomib subcutaneously (SC) or intravenously (IV) over 3-5 seconds on days 1, 8, and 15; cyclophosphamide orally (PO) once daily (QD) on days 1-21; and dexamethasone PO on days 1, 8, and 15. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 3 months.

Official Title
-----------------
A Phase II Trial of Weekly Bortezomib and Dexamethasone With Oral Metronomic Cyclophosphamide in Elderly Patients With Plasma Cell Myeloma

Conditions
-----------------
Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: bortezomib
* Drug: cyclophosphamide
* Drug: dexamethasone
* Other: laboratory biomarker analysis
* Other: quality-of-life assessment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have a confirmed diagnosis of symptomatic myeloma in accordance with International Myeloma Working group (IMWG) criteria Bone marrow plasmacytosis with > 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma Symptomatic disease, i.e., end-organ damage due to multiple myeloma (MM) including at least one of the following: anemia, hypercalcemia, bone disease (lytic bone lesions or pathologic fracture), or renal dysfunction Absolute neutrophil count (ANC) >= 1000 cells/mm^3 (without use of growth factors) Platelets >= 50,000 cells/mm^3 Direct bilirubin =< 1.5 X upper limit of normal (ULN); elevated bilirubin is permissible if patient has a known history of elevated bilirubin due to Gilbert's or if elevated bilirubin is due to hemolysis Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 X ULN Subjects must have the ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Prior treatment with > 1 cycle of any plasma cell myeloma (PCM) induction regimen (maximum 6 weeks of prior treatment) Prior radiation therapy is allowed Prior treatment for other cancers is allowed as long as patient meets criteria for adequate hematopoietic and organ function and is not actively on chemotherapy for another cancer Grade >= 2 peripheral neuropathy Second malignancy currently undergoing chemotherapy or radiotherapy; hormonal therapy for breast or prostate cancer is allowed Patients may not be receiving any other investigational agents History of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib, cyclophosphamide, dexamethasone or other agents used in this study Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (bortezomib, cyclophosphamide, dexamethasone)<br>Patients receive bortezomib SC or IV over 3-5 seconds on days 1, 8, and 15; cyclophosphamide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. | Drug: bortezomib<br>* Given SC or IV<br>* Other names: VELCADE;Drug: cyclophosphamide<br>* Given PO<br>* Other names: Endoxana;Drug: dexamethasone<br>* Given PO<br>* Other names: DXM;Other: laboratory biomarker analysis<br>* Optional correlative studies<br>Other: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response rate in accordance with the IMWG Uniform Response criteria | The number of people with any response as defined by the IMWG criteria | Up to 7 months | 
| Incidence of toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4 |  | Up to 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General | Changes in quality of life at baseline to the end of treatment estimated by means with confidence intervals. Quality of life will be assessed using the 34 item general functional assessment of cancer therapy (FACT-G) questionnaire. | Up to 24 weeks | 
| Changes in functional status | Changes in functional status at baseline to the end of treatment estimated by means with confidence intervals. Functional status will be assessed by scoring the thirteen item Vulnerable Elders Survey (VES-13). | Up to 24 weeks | 
| Overall Survival | The number of people alive after 24 weeks on the study | 24 Weeks | 
| Changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General | Average changes in quality of life at baseline estimated by means with confidence intervals.Quality of life will be assessed using the 34 item general functional assessment of cancer therapy (FACT-G) questionnaire. | After 6 weeks (2 courses) of treatment | 
| Changes in functional status | Changes in functional status at baseline to the second course 2 of therapy estimated by means with confidence intervals. Functional status will be assessed by scoring the thirteen item Vulnerable Elders Survey (VES-13). | After 6 weeks (2 courses) of treatment |