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

Stage III Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02082405
• Other study ID #: CASE3A13
• Secondary ID: NCI-2014-00250CA
• Status: Withdrawn
• Phase: Phase 2
• First received: March 6, 2014
• Last updated: April 23, 2015
• Start date: April 2015

Study information

• Verified date: April 2015
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Stage I Multiple Myeloma
• Stage II Multiple Myeloma
• Stage III Multiple Myeloma

Intervention

Drug:
• bortezomib
Given SC or IV
• cyclophosphamide
Given PO
• dexamethasone
Given PO

Other:
• laboratory biomarker analysis
Optional correlative studies
• quality-of-life assessment
Ancillary studies

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Incidence of toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4		Up to 7 months	Yes
Secondary	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	No
Secondary	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	No
Secondary	Overall Survival	The number of people alive after 24 weeks on the study	24 Weeks	No
Secondary	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	No
Secondary	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	No