Bortezomib, Dexamethasone, and Cyclophosphamide in Treating Older Patients With Multiple Myeloma
Primary Purpose
Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
bortezomib
cyclophosphamide
dexamethasone
laboratory biomarker analysis
quality-of-life assessment
Sponsored by
About this trial
This is an interventional treatment trial for Stage I Multiple Myeloma
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (bortezomib, cyclophosphamide, dexamethasone)
Arm Description
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.
Outcomes
Primary Outcome Measures
Overall Response rate in accordance with the IMWG Uniform Response criteria
The number of people with any response as defined by the IMWG criteria
Incidence of toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4
Secondary Outcome Measures
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.
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).
Overall Survival
The number of people alive after 24 weeks on the study
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.
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).
Full Information
NCT ID
NCT02082405
First Posted
March 6, 2014
Last Updated
April 23, 2015
Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02082405
Brief Title
Bortezomib, Dexamethasone, and Cyclophosphamide in Treating Older Patients With Multiple Myeloma
Official Title
A Phase II Trial of Weekly Bortezomib and Dexamethasone With Oral Metronomic Cyclophosphamide in Elderly Patients With Plasma Cell Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Withdrawn
Why Stopped
Funding unavailable
Study Start Date
April 2015 (undefined)
Primary Completion Date
August 2016 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (bortezomib, cyclophosphamide, dexamethasone)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
LDP 341, MLN341, VELCADE
Intervention Description
Given SC or IV
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Other Intervention Name(s)
Aeroseb-Dex, Decaderm, Decadron, DM, DXM
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Optional correlative studies
Intervention Type
Other
Intervention Name(s)
quality-of-life assessment
Other Intervention Name(s)
quality of life assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Overall Response rate in accordance with the IMWG Uniform Response criteria
Description
The number of people with any response as defined by the IMWG criteria
Time Frame
Up to 7 months
Title
Incidence of toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4
Time Frame
Up to 7 months
Secondary Outcome Measure Information:
Title
Changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General
Description
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.
Time Frame
Up to 24 weeks
Title
Changes in functional status
Description
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).
Time Frame
Up to 24 weeks
Title
Overall Survival
Description
The number of people alive after 24 weeks on the study
Time Frame
24 Weeks
Title
Changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General
Description
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.
Time Frame
After 6 weeks (2 courses) of treatment
Title
Changes in functional status
Description
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).
Time Frame
After 6 weeks (2 courses) of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erica Campagnaro
Organizational Affiliation
Case Comprehensive Cancer Center
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Bortezomib, Dexamethasone, and Cyclophosphamide in Treating Older Patients With Multiple Myeloma
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