Bone Effect of Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma

This study has been terminated.
(Slow accrual; PI left primary institution)
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT01062230
First received: February 2, 2010
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

The primary aim of this trial is to determine the effect of a short course (i.e., 3 cycles) of low-dose Bortezomib (Velcade) on bone remodeling and on disease progression. The dose of bortezomib used in this trial of 0.7 mg/m2 is the lowest dose which has shown efficacy in the 3 largest monotherapy trials with bortezomib. 17% of patients in the APEX, 9% patients in CREST and 24% in SUMMIT trials were treated with 0.7 mg/m2 dosages. Bortezomib will be given on days 1, 8, 15, 22 over 42 days to reduce the incidence of possible drug related side effects.

OBJECTIVES:

Primary Objective

The primary objective of this study is to:

  • To evaluate the effect of Velcade at 0.7 mg/m2 dose on inducing osteoblast activation as measured by ALP and other bone markers in patients with relapsed/refractory myeloma.

Secondary Objectives

The secondary objectives of this study are to:

  • To evaluate the association between osteoblastic activation and myeloma response to Velcade.
  • To identify predictive factors for Velcade-associated osteoblastic activation.

Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib (Velcade)
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bone Effect of Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • To evaluate the effect of Velcade at 0.7 mg/m2 dose on inducing osteoblast activation as measured by ALP and other bone markers in patients with relapsed/refractory myeloma. [ Time Frame: January 2012 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the association between osteoblastic activation and myeloma response to Velcade. [ Time Frame: January 2012 ] [ Designated as safety issue: No ]
  • To identify predictive factors for Velcade-associated osteoblastic activation. [ Time Frame: January 2012 ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: January 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All patients
All participants enrolled.
Drug: Bortezomib (Velcade)

Bortezomib will be administered as a 3-5 second bolus IV injection at the dose of 0.7 mg/m2 on days 1, 4, 8, and 11 q. 21 days times three cycles.

Patients will undergo three 21-day cycles.

Other Name: Velcade

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. History of histologically documented MM with relapsed or progressive disease after at least one line of prior therapy.
  2. Patient has measurable disease in which to capture response, defined as one or more of the following:

    1. Serum M-protein level > 1.0 gm/dl (10.0 g/L) measured by serum protein electrophoresis or immunoglobulin electrophoresis; or
    2. Urinary M-protein excretion > 200 mg/24 hrs; or
    3. Bone marrow plasmacytosis of > 30% by bone marrow aspirate and/or biopsy; or
    4. Serum Free Light Chains (By the Freelite test) > 2X ULN, in the absence of renal failure
    5. Radiographic evidence of disease
  3. Performance status of < 2 as per ECOG scale, unless PS of 3-4 based solely on bone pain.
  4. Patients must have a platelet count > 100,000/L and an ANC of at least 1,000/μl.
  5. Patients must have adequate renal function defined as serum creatinine ≤2.5 mg/dL.
  6. Patients must have adequate hepatic function defined as serum transaminases and direct bilirubin < 3 x the upper limit of normal.
  7. Male or female adults of at least 18 years of age.
  8. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  9. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
  10. Growth factors are allowed during the study
  11. Male subject agrees to use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

  1. Platelet count of <100x 10(9)/L within 14 days before enrollment.
  2. Absolute neutrophil count (ANC) <1.0 x 10(9)/L
  3. Serum creatinine ≥ 2.5 mg/dL within 14 days before enrollment.
  4. Patient has >Grade 2 peripheral neuropathy within 14 days before enrollment.
  5. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 1.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  6. Patients with a history of treatment for clinically significant ventricular cardiac arrhythmias.
  7. Patient has hypersensitivity to bortezomib, boron or mannitol.
  8. Chemotherapy or radiotherapy received within the previous 4 weeks of study enrollment.
  9. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  10. Patient has received other investigational drugs with 14 days before enrollment
  11. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  12. Diagnosed or treated for another malignancy within 3 years 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.
  13. POEMS Syndrome
  14. Clinically significant hepatic dysfunction as noted by bilirubin or AST > 3 times the upper normal limit or clinically significant concurrent hepatitis.
  15. Uncontrolled, active infection
  16. Patients that have taken bisphosphonates within 30 days of screening will not be eligible for this trial.
  17. Must not have received VELCADE 90 days prior to enrolling in this trial.
  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: NCT01062230

Locations
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Arkansas
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Maurizio Zangari, MD University of Arkansas
  More Information

No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT01062230     History of Changes
Other Study ID Numbers: HCI35813
Study First Received: February 2, 2010
Last Updated: July 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Arkansas:
Cancer
Hematologic malignancy

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
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014