Study of Velcade® and Bone Formation in Patients With Relapsed/Refractory Multiple Myeloma

NCT00128921 | Terminated Phase 2 Results DMC

• 1 other identifier: UARK 2004-22
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Velcade (bortezomib, PS-341) has recently been approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma for patients who have received at least one prior therapy. Velcade is a unique compound developed by scientists at Millennium Pharmaceuticals, Inc. Velcade enters cells and affects the way they divide. Cancer cells are particularly sensitive. Velcade interferes with the enzyme "proteasome" which is responsible for allowing cells to divide. When cancer cells cannot divide, they die. Velcade falls into the class of drugs known as "proteasome inhibitors."

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (5)

• Number of Participants With a Positive Response to Bortezomib Measured by the Bone Marker Parathyroid Hormone

  Parathyroid hormone: Any increase in PTH was considered response

  6 months

• Number of Participants With a Positive Response to Bortezomib Measured by Bone Markers Like Calcium

  Calcium: any Calcium increase would refer to a positive response.

  6 months

• Number of Participants With a Positive Response to Bortezomib Measured by Bone Marker Alkaline Phosphatase

  Alkaline phosphatase: If the Alkaline phosphatase increases it's considered positive response

  6 months

• Number of Participants With a Positive Response to Bortezomib Measured by Bone Markers Like Magnesium

  Magnesium: Any Magnesium increase would refer to a positive response.

  6 months

• Number of Participants With a Positive Response to Bortezomib Measured by Bone Markers Like Phosphate.

  Phosphate: any Phosphate increase would refer to a positive response.

  6 months

Secondary Outcomes (1)

• Number of Participants With a Positive Response to Bortezomib Measured by Bone Marker Osteocalcin

  6 months

Study Arms (3)

Velcade, Cohort A

EXPERIMENTAL

Treatment: 1.3 mg/m\^2

Drug: VELCADE™

Velcade, Cohort B

EXPERIMENTAL

Treatment: 1.0 mg/m\^2

Drug: VELCADE™

Velcade, Cohort C

EXPERIMENTAL

Treatment: 0.7 mg/m\^2

Drug: VELCADE™

Interventions

VELCADE™ DRUG

Patients will receive two cycles of VELCADE™ (1.3 mg/m2, 1.0 mg/m2 or 0.7 mg/m2) on days 1, 4, 8, and 11, on a 21 day cycle. No growth factors or bisphosphonates will be allowed during study treatment. Bone markers will be measured: Days 1, 4, 8, 11: Pre-dose, post-dose, and every 2-4 hours for 8 hours Days 2-3, 5-7, 9-10, 12-21: every 24 hours, beginning with the immediate post-dose sample (+/- 2 hours) Other laboratory and radiologic studies will be performed as detailed in the Study Calendar. Patients will complete the study after two cycles of VELCADE™. However, if a patient continues to receive VELCADE™ as part of his/her treatment for relapsing MM, routine bone markers may be monitored for the duration of VELCADE™ treatment as clinically indicated.

Also known as: Bortezomib

Velcade, Cohort A; Velcade, Cohort B; Velcade, Cohort C

Eligibility Criteria

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

You may qualify if:

• History of histologically documented MM with relapsed or progressive disease after at least one line of prior therapy.
• Patient has measurable disease in which to capture response, defined as one or more of the following:
• Serum M-protein level \> 1.0 gm/dl (10.0 g/L) measured by serum protein electrophoresis or immunoglobulin electrophoresis; or
• Urinary M-protein excretion \> 1000 mg/24 hours; or
• Bone marrow plasmacytosis of \> 30% by bone marrow aspirate and/or biopsy; or
• Serum free light chains (by the Freelite test) \> 2 X the upper limit of normal, in the absence of renal failure.
• Evidence of active disease by radiographic techniques
• Performance status (PS) of \<= 2 as per Southwest Oncology Group scale, unless PS of 3-4 based solely on bone pain.
• Patients must have a platelet count \>= 50,000/mm3, and an absolute neutrophil count of at least 1,000/μl.
• Patients must have adequate renal function defined as creatinine clearance \> 30ml/min.
• Patients must have adequate hepatic function defined as serum transaminases and direct bilirubin \< 2 X the upper limit of normal.
• Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy test documented within one week of registration. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Male or female adults of at least 18 years of age.
• Patients must have signed and Institutional Review Board approved written informed consent form and demonstrate willingness to meet follow-up schedule and study procedure obligations

You may not qualify if:

• Chemotherapy or radiotherapy received within the previous 4 weeks.
• Has received previous bortezomib therapy
• Significant neurotoxicity, defined as grade \> 2 neurotoxicity per National Cancer Institute Common Toxicity Criteria.
• Platelet count \< 50,000/mm3, or ANC \< 1,000/μl
• Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome.
• Patient has hypersensitivity to bortezomib, boron, or mannitol
• Clinically significant hepatic dysfunction as noted by bilirubin or AST \>3 times the upper normal limit or clinically significant concurrent hepatitis.
• New York Hospital Association Class III or Class IV heart failure.
• Myocardial infarction within the last 6 months.
• Non-secretory multiple myeloma, unless the patient has measurable lesions on computed tomography, magnetic resonance imaging and/or positron emission tomography.
• Uncontrolled, active infection.
• Patients with a history of treatment for clinically significant ventricular cardiac arrhythmias.
• Poorly controlled hypertension, diabetes mellitus, or other serious or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
• Pregnant or potential for pregnancy. Women of childbearing potential will have a pregnancy \[beta-HCG\] test at screening, and will be required to use a medically approved contraceptive method. Pregnancy testing will be performed prior to administration of each cycle of study drug.
• Breast-feeding women may not participate.

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Links

• Click here for more information about A Phase II Dose-Response Study of Velcade®

MeSH Terms

Conditions

Multiple Myeloma

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

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Early termination due to difficulty in accruing participants.

Results Point of Contact

• Title: Nathan M. Petty
• Organization: University of Arkansas for Medical Sciences, Myeloma Institute

pettynathanm@uams.edu

501-526-6990

Study Officials

• Maurizio Zangari, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2005
• First Posted: August 10, 2005
• Study Start: April 1, 2006
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: April 26, 2012
• Results First Posted: April 26, 2012

Record last verified: 2012-04

Locations

US (1)