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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Nikhil Munshi, M.D., Boston VA Research Institute, Inc.
ClinicalTrials.gov Identifier:
NCT01090921
First received: March 15, 2010
Last updated: February 4, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib + Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study to Evaluate Efficacy and Safety of Single Weekly Administration of Bortezomib in Newly Diagnosed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Boston VA Research Institute, Inc.:

Primary Outcome Measures:
  • To evaluate the objective response rate (CR + PR) to 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. [ Time Frame: Approximately 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. [ Time Frame: Approximately 3 years ] [ Designated as safety issue: Yes ]
  • To evaluate time to progression and duration of response following bortezomib + dexamethasone treatment in patients with newly diagnosed multiple myeloma who are either ineligible or wish to postpone SCT. [ Time Frame: Approximately 3 years ] [ Designated as safety issue: Yes ]
  • To collect blood and marrow samples for future analysis of molecular markers associated with response or resistance to bortezomib + dexamethasone in patients with newly diagnosed myeloma who are either ineligible or wish to postpone SCT. [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: May 2007
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single-Arm Drug: Bortezomib + Dexamethasone

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 Name: Velcade

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01090921

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

No publications provided

Responsible Party: Nikhil Munshi, M.D., Principal Invesetigator -- Coordinating Site, Boston VA Research Institute, Inc.
ClinicalTrials.gov Identifier: NCT01090921     History of Changes
Other Study ID Numbers: X05153
Study First Received: March 15, 2010
Last Updated: February 4, 2013
Health Authority: United States: VA Boston Institutional Review Board

Keywords provided by Boston VA Research Institute, Inc.:
Multiple Myeloma
Bortezomib
Newly diagnosed
Newly diagnosed Multiple Myeloma

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
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on August 18, 2014