Autophagy Induction After Bortezomib for Myeloma

• ClinicalTrials.gov Identifier: NCT01594242
• Recruitment Status: Completed
• First Posted: May 9, 2012
• Last Update Posted: April 16, 2019
• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Information provided by (Responsible Party): Abramson Cancer Center of the University of Pennsylvania

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Bortezomib	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 0 Study of Autophagy Induction After Bortezomib For Myeloma
• Actual Study Start Date: July 10, 2012
• Actual Primary Completion Date: March 2, 2015
• Actual Study Completion Date: March 2, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Adverse Events [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Pennsylvania

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Abramson Cancer Center of the University of Pennsylvania

Investigators

• Principal Investigator: Dan Vogl, MD; Abramson Cancer Center of the University of Pennsylvania

More Information

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01594242
• Other Study ID Numbers: UPCC 05411
• First Posted: May 9, 2012
• Last Update Posted: April 16, 2019
• Last Verified: April 2019

Keywords provided by Abramson Cancer Center of the University of Pennsylvania:

multiple myeloma; bortezomib; proteasome inhibitor

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Bortezomib; Antineoplastic Agents