Subcutaneous (SC) Bortezomib-Regimens for Patients With RR MM Failing Prior IV Bortezomib-Containing Regimens

NCT01695330 | Terminated Phase 2 Results DMC

• 1 other identifier: X05384
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2, multicenter, open label, nonrandomized study for patients with MM who will receive treatment with a SC bortezomib-containing combination regimen that does not contain thalidomide or vincristine. The patients will be required to have received a prior IV bortezomib containing combination regimen that did not contain thalidomide or vincristine and that differs from the SC bortezomib-containing one. In between the time that the patient received the IV bortezomib-based combination regimen and enrollment onto this study, patients may have received other non-bortezomib-based regimens as long as these treatments did not contain thalidomide or vincristine. This study will enroll patients who have relapsed or have become refractory to their prior IV-administered bortezomib-containing combination regimen as demonstrated by progressive disease while on or following that regimen. Patients must have received 4 doses of a minimum of 1.0 mg/m2 of bortezomib administered IV in no more than 4 weeks per cycle. Patients must have received at least one cycle meeting this definition and have shown progressive disease to be considered eligible. Patients who have relapsed or have become refractory to their most recent IV bortezomib-containing combination regimen are eligible regardless of when they received that regimen, as long as they meet the above criteria. The study will consist of a screening period, followed by up to eight open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment cycle, and a follow-up period.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Relapsed; Refractory; Bortezomib; Subcutaneous; Oncotherapeutics

Outcome Measures

Primary Outcomes (1)

• The Primary Objective of This Study Will be to Investigate the Incidence and Severity of Peripheral Neuropathy Caused by a Prior Intravenous VELCADE-containing Regimen in Comparison to That Caused by a Subcutaneous VELCADE-containing Regimen.

  Definition of incidence: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit. Definition of severity: the severity of any treatment-emergent peripheral neuropathy experienced by a patient on-study. Peripheral neuropathy severity is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as the End of Study visit and is graded on a 0-4 scale based on CTCAE criteria. Incidence of Peripheral Neuropathy Definition: the number of participants enrolled in the study experiencing treatment-emergent peripheral neuropathy. Emergence of peripheral neuropathy is determined via neurological assessment conducted on Day 1 and Day 11 of each treatment cycle as well as during the End of Study visit.

  Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.

Secondary Outcomes (1)

• Compare Overall Response Rate (CR + VGPR + PR + MR), Compare Disease Parameters, & Determine Incidence and Severity of Injection-site Reactions.

  Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28 day treatment cycles.

Study Arms (1)

Subcutaneous bortezomib

EXPERIMENTAL

Drug: Subcutaneous bortezomib

Interventions

Subcutaneous bortezomib DRUG

Bortezomib will be administered SC at a dose of 1.0 mg/m2. Doses are to be administered on days 1, 4, 8, and 11 of a 28-day cycle. All other drugs used in combination with the SC bortezomib as well as their doses and schedules will be at the discretion of the Principal Investigator.

Also known as: Velcade

Subcutaneous bortezomib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a diagnosis of MM based on the following:
• Major crit.:
• plasmacytomas on tissue biopsy
• bone marrow plasmacytosis (\> 30% plasma cells)
• m-spike on serum electrophoresis IgG \> 3.5 g/dL or IgA \> 2.0 g/dL; kappa or lambda light chain excretion \> 1 g/day on 24 hour urine protein electrophoresis
• Minor crit.:
• bone marrow plasmacytosis (10% to 30% plasma cells)
• monoclonal Ig present but of lesser magnitude than given under major crit.
• lytic bone lesions
• normal IgM \< 50 mg/dL, IgA \< 100 mg/dL, or IgG \< 600 mg/dL
• Any of the following sets of crit. will confirm the diagnosis of MM:
• any 2 of the major crit.
• major criterion 1 plus minor criterion 2, 3, or 4
• major criterion 3 plus minor criterion 1 or 3
• minor crit. 1, 2, and 3, or 1, 2, and 4

You may not qualify if:

• POEMS syndrome
• PCL
• Primary amyloidosis
• Diagnosed or treated for another malignancy w/in 3 yrs of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• ≤ Grade 2 peripheral neuropathy
• Pt had myocardial infarction w/in 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Severe hypercalcemia, i.e., serum calcium ≤ 12 mg/dL (3.0 mmol/L) corrected for albumin
• Undergone major surgery w/in 28 days prior enrollment or has not recovered from side effects of such therapy (see protocol)
• Received the following prior therapy:
• Thalidomide or vincristine alone or as part of a treatment regimen administered between the last IV bort.-based regimen and Cycle 1, Day 1 on this study. However, prior exposure to thalidomide or vincristine is allowed.
• Chemotherapy w/in 21 days of study drugs (6 weeks for nitrosoureas)
• Corticosteroids (\>10 mg/day prednisone or equivalent) w/in 21 days of study drugs unless steroids are being administered at that dose or greater as part of the new regimen
• Immunotherapy or antibody therapy as well as lenalidomide, arsenic trioxide or bort. w/in 21 days before study drugs
• Radiation therapy w/in 21 days before study drugs. (see protocol for exceptions)
• Use of any other experimental drug or therapy w/in 28 days of study drugs

Sponsors & Collaborators

• Oncotherapeutics: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

James R. berenson, M.D., Inc.

West Hollywood, California, 90069, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. James Berenson
• Organization: Oncotherapeutics

jberenson@berensonocology.com

310-420-9649

Study Officials

• James R Berenson, MD

  James R. Berenson, M.D., Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2012
• First Posted: September 27, 2012
• Study Start: May 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: January 16, 2017
• Results First Posted: January 16, 2017

Record last verified: 2016-11

Locations

US (1)