Clinical trial NCT02082405: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-03-10
Enrollment: 0
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Response rate in accordance with the IMWG Uniform Response criteria
timeFrame: Up to 7 months
measure: Incidence of toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4
timeFrame: Up to 7 months
Secondary outcomes:
measure: Changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General
timeFrame: Up to 24 weeks
measure: Changes in functional status
timeFrame: Up to 24 weeks
measure: Overall Survival
timeFrame: 24 Weeks
measure: Changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General
timeFrame: After 6 weeks (2 courses) of treatment
measure: Changes in functional status
timeFrame: After 6 weeks (2 courses) of treatment
Other outcomes:
Locations:
Study officials:
affiliation: Case Comprehensive Cancer Center
name: Erica Campagnaro
role: PRINCIPAL_INVESTIGATOR
References: