Safety and Efficacy Study of Single Weekly Bortezomib in Newly Diagnosed Multiple Myeloma

Phase II Study to Evaluate Efficacy and Safety of Single Weekly Administration of Bortezomib in Newly Diagnosed Multiple Myeloma

This is a research study to see if a new drug called bortezomib is useful to treat multiple myeloma in people who are newly diagnosed, and have not yet received treatment for their disease. VELCADE® (bortezomib) for Injection is a drug under development by Millennium Pharmaceuticals, Inc.

Study Overview

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

Detailed Description

This study is a multi-site study which will enroll up to 50 patients with multiple myeloma who have not had prior treatment.

Prior to starting treatment individuals will be evaluated to determine if they are eligible to participate in the study. There are certain prestudy test that are required: physical exam, blood tests, ECG, chest x-ray, skeletal survey, bone marrow aspirate and biopsy to confirm the diagnosis of multiple myeloma and to determine baseline health status.

Before beginning each treatment cycle and at the end of the study, patients will have protein studies (including blood and urine) to see if they are responding to the treatment. Before each weekly treatment cycle patients will also have blood tests for red and white blood cells and platelets, and blood chemistry tests for electrolytes, kidney and liver function, calcium and blood sugar.

Patients may receive up to 6 cycles of treatment. At the end of the study, individuals who have responded to treatment will be seen every two months to check for disease progression.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock VA Medical Center
  • California
    • Los Angeles, California, United States, 90073
      • West Los Angeles VA Medical Center
    • San Francisco, California, United States, 94121
      • San Francisco VA Medical Center
  • Colorado
    • Denver, Colorado, United States, 80220
      • Eastern Colorado Health Care System
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • West Haven VA Medical Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Tampa VA Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30033
      • Atlanta VA Medical Center
  • Massachusetts
    • Jamaica Plain, Massachusetts, United States, 02130
      • VA Boston Healthcare System
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15240
      • Pittsburgh VA Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center

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:

1. Diagnosis of multiple myeloma based on standard criteria.
2. Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of > 1Gm/dL and/or urine monoclonal immunoglobulin spike of > 200mg/24 hours.
3. Non-secretors must have measurable protein by Freelite or measurable disease such as plasmacytoma to be eligible.
4. Patient must not have been previously treated with chemotherapy. Prior treatment of hypercalcemia with corticosteroids, or bisphosphonates does not disqualify the patient.

5. Patient must be ineligible for autologous stem cell transplant due to one or more of the following reasons:

   • Age>65
   • Impaired renal function (creatinine≥2.0 mg/dL)
   • Impaired pulmonary function (DLCO≤50%)
   • Poor performance status (KPS≤80)

   • Other prohibitive comorbid disorder

     • 5b. Patients≥60 who decline autologous stem cell transplant are eligible for this study.
     • 5c. Patients who are eligible but wish to postpone autologous stem cell transplant are eligible for this study.
6. Karnofsky performance status>50
7. Patients treated with local radiotherapy with or without a brief exposure to steroids are eligible. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed, followed by a four week wash out period Spot RT to ≤3 vertebrae acceptable prior to entry.

8. Meets the following pretreatment laboratory criteria at Baseline (Within 14 days prior to study drug administration):

   1. Platelet count>50x10^9/L or, if the bone marrow is extensively infiltrated,>30x10^9/L
   2. Hemoglobin>8.0G/dL
   3. Absolute neutrophil count >1.0x10^9/L or, if the bone marrow is extensively infiltrated, >0.5x10^9/L

9. Meets the following pretreatment laboratory criteria for liver function tests at the screening visit conducted within 14 days of registration

   1. AST (SGOT): <3 times the upper limit of institutional laboratory normal
   2. ALT (SGPT): <3 times the upper limit of institutional laboratory normal
   3. Total bilirubin: <2 times the upper limit of institutional laboratory normal, unless clearly related to the disease
10. Women with child-bearing potential should be practicing an adequate form of contraception, as judged by the investigator (i.e. birth control pills, double barrier method, abstinence, etc.) or be surgically sterile or 12 months post-menopausal. Male subject agrees to use an acceptable method for contraception for the duration of the study.
11. Age 18 years or older
12. Has given voluntary written informed consent.

Exclusion Criteria:

1. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes)
2. Plasma cell leukemia
3. Impaired kidney function requiring dialysis, patients on hemodialysis are excluded
4. Receiving steroids >the equivalent of 10mg prednisone daily for other medical conditions, e.g., asthma, systemic lupus erythematosis, rheumatoid arthritis
5. Infection not controlled by antibiotics
6. HIV infection. Patients should provide consent for HIV testing according to the institution's standard practice
7. Known active hepatitis B or C
8. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix D), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
9. Second malignancy requiring concurrent treatment
10. Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
11. Positive pregnancy test in women of childbearing potential
12. Patient has hypersensitivity to boron or mannitol.
13. Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.
14. Patient has received other investigational drugs with 14 days before enrollment

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: Single-Arm; Bortezomib is administered at a dose of 1.6mg/m2 IV push over 3 to 5 seconds. Treatment is administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone is also administered at a dose of 40mg daily on day of and day after each dose of Bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone. The study duration for a given subject will be approximately 30 weeks.

Drug: Bortezomib; Bortezomib will be administered at a dose of 1.6 mg/m2 IV push. Treatment will be administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone will also be administered at a dose of 40mg on the day of and day after each dose of bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone.; Other Names: Velcade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants at Each Response Category (Stable Disease, Minimal Response, Partial Response, Very Good Partial Response, Near Complete Response/Complete Resonse)	To evaluate the response rate for weekly administered bortezomib + dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant or who are eligible but wish to postpone autologous stem cell transplant.	Data was collected for each subject for the duration of the participation in the study, which was an average of 4.8 cycles.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Reductions in Bortezomib, Dexamethasone or Both	To evaluate the toxicity (safety and tolerability) of weekly bortezomib + dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant or who are eligible but wish to postpone autologous stem cell transplant.	Data was collected for each subject for the duration of the participation in the study, which was an average of 4.8 cycles.

Collaborators and Investigators

• Sponsor: Boston VA Research Institute, Inc.
• Collaborators: Millennium Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Nikhil C. Munshi, M.D., Boston VA Research Institute, Inc.; Study Chair: Saem Lee, Boston VA Research Institute, Inc.

Publications and helpful links

General Publications

• Girnius SK, Lee S, Kambhampati S, Rose MG, Mohiuddin A, Houranieh A, Zimelman A, Grady T, Mehta P, Behler C, Hayes TG, Efebera YA, Prabhala RH, Han A, Yellapragada SV, Klein CE, Roodman GD, Lichtenstein A, Munshi NC. A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation. Br J Haematol. 2015 Apr;169(1):36-43. doi: 10.1111/bjh.13243. Epub 2015 Jan 8.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (ACTUAL): March 1, 2015
• Study Completion (ACTUAL): March 1, 2015

Study Registration Dates

• First Submitted: March 15, 2010
• First Submitted That Met QC Criteria: March 19, 2010
• First Posted (ESTIMATE): March 23, 2010

Study Record Updates

• Last Update Posted (ACTUAL): September 9, 2020
• Last Update Submitted That Met QC Criteria: August 23, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Bortezomib; Newly diagnosed; Newly diagnosed Multiple Myeloma
• 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: X05153

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO