Clinical trial NCT01594242: Autophagy Induction After Bortezomib for Myeloma
Official title: A Phase 0 Study of Autophagy Induction After Bortezomib For Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Multiple Myeloma
Keywords: multiple myeloma
bortezomib
proteasome inhibitor
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2012-05-09
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients who are planned to start a bortezomib-containing regimen (whether for newly diagnosed or relapsed myeloma) will begin with one week off therapy and then one week of single agent bortezomib to allow investigation of its effects on cellular metabolism. Patients may then go on to receive bortezomib in whatever combination is planned by their treating oncologist.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to better understand the effects of the chemotherapy medication bortezomib on cancer cells. The investigators are therefore taking blood and bone marrow samples from patients with myeloma who are receiving bortezomib to see if the investigators can detect autophagy in the myeloma cells from the bone marrow and in immune cells in the blood. Subjects are eligible if their doctor is planning to treat them with bortezomib for the first time for their myeloma.

Detailed description: PRIMARY OBJECTIVE:

The primary objective of this study is to determine whether administration of bortezomib leads to an increase in cellular autophagy, as determined by electron micrographs of peripheral blood lymphocytes and primary myeloma cells in patients receiving single-agent bortezomib.

SECONDARY OBJECTIVES

1. To determine the optimal timing of autophagy assessments for patients receiving bortezomib.
2. To explore whether high levels of autophagy are associated with resistance to bortezomib therapy.
3. To validate our primary assay by confirming baseline stability of the number of autophagic vesicles per cell
4. To compare results of autophagy measurements in peripheral blood mononuclear cells and bone marrow plasma cells

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed multiple myeloma (both newly diagnosed and relapsed patients are permitted)
* No more than one line of prior therapy containing bortezomib. No prior therapy with any other proteasome inhibitor.
* For subjects who received previous bortezomib, at least a partial response while on the bortezomib-containing therapy, without progression while on bortezomib-containing therapy or within 90 days of stopping bortezomib.
* Planned therapy, as determined by the patient's treating physician, with a bortezomib-containing regimen
* Medically suitable to undergo study procedures, including a one-week washout of prior therapy, one week of observation, and one week of single-agent bortezomib
* Provision of written informed consent

Exclusion Criteria

* Age \<18 years (though the demographics of myeloma make it highly unlikely that any children will meet inclusion criteria)
* Treatment with other anti-myeloma agents, including corticosteroids, thalidomide, or lenalidomide, within the 7 days prior to the study baseline bone marrow biopsy.
* Inability to understand the informed consent document or unwillingness to consent.
* Written informed consent must be obtained from all patients before study entry.

Primary outcomes:
measure: Number of Adverse Events
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Dan Vogl, MD
role: PRINCIPAL_INVESTIGATOR
References: