Autophagy Induction After Bortezomib for Myeloma

Abramson Cancer Center at Penn Medicine

Status and phase: Completed; Early Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Bortezomib

Study type: Interventional

Funder types: Other

Identifiers

NCT01594242

UPCC 05411

Details and patient eligibility

About

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.

Full 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

Enrollment: 11 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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11 participants in 1 patient group

Autophagy Induction After Bortezomib

Experimental group

Description:

Subjects will undergo a baseline bone marrow aspirate and biopsy (under sedation if preferred by the subject) and have baseline blood samples (and urine samples if clinically indicated for measurement of their myeloma). The following week, subjects will undergo a second bone marrow aspirate and biopsy and have additional blood samples taken for research assays prior to starting therapy on treatment day 1 with bortezomib at the standard dose of 1.3 mg/m2. Subjects will receive a second dose of bortezomib on treatment day 4, followed by a third bone marrow aspirate and biopsy on treatment day 4 or 5, along with serial blood samples on treatment days 4 and 5. After completion of the week of study treatment, subjects may continue treatment with the bortezomib-containing regimen planned by their treating oncologist. Active study participation will end after the completion of the week of study treatment.

Treatment:

Drug: Bortezomib