Autophagy Induction After Bortezomib for Myeloma

A Phase 0 Study of Autophagy Induction After Bortezomib For Myeloma

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bortezomib

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

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Autophagy Induction After Bortezomib; 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.

Drug: Bortezomib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Adverse Events	2 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center of the University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2012
• Primary Completion (Actual): March 2, 2015
• Study Completion (Actual): March 2, 2015

Study Registration Dates

• First Submitted: April 19, 2012
• First Submitted That Met QC Criteria: May 8, 2012
• First Posted (Estimate): May 9, 2012

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 12, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: bortezomib; multiple myeloma; proteasome inhibitor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: UPCC 05411