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

NCT01062230 | Terminated Phase 2 Results DMC

• 1 other identifier: HCI35813
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

Cancer; Hematologic malignancy

Outcome Measures

Primary Outcomes (1)

• Maximum Percent Change From Baseline in Intact Parathyroid Hormone Levels on Day 1

  All patients received 0.7 mg/m2 of bortezomib on days 1, 4, 8 and 11 of a 21 day cycle, for maximum of three cycles for an average of 18 months. Intact Parathyroid hormone was measured in patients with relapsed/refractory myeloma for osteoblast activation. Other bone markers were examined using similar methods.

  Baseline and Day 1

Study Arms (1)

All patients

EXPERIMENTAL

All participants enrolled.

Drug: Bortezomib (Velcade)

Interventions

Bortezomib (Velcade) DRUG

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.

Also known as: Velcade

All patients

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 \> 200 mg/24 hrs; or
• Bone marrow plasmacytosis of \> 30% by bone marrow aspirate and/or biopsy; or
• Serum Free Light Chains (By the Freelite test) \> 2X ULN, in the absence of renal failure
• Radiographic evidence of disease
• Performance status of \< 2 as per ECOG scale, unless PS of 3-4 based solely on bone pain.
• Patients must have a platelet count \> 100,000/L and an ANC of at least 1,000/μl.
• Patients must have adequate renal function defined as serum creatinine ≤2.5 mg/dL.
• Patients must have adequate hepatic function defined as serum transaminases and direct bilirubin \< 3 x the upper limit of normal.
• Male or female adults of at least 18 years of age.
• 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.
• 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.
• Growth factors are allowed during the study

You may not qualify if:

• Platelet count of \<100x 10(9)/L within 14 days before enrollment.
• Absolute neutrophil count (ANC) \<1.0 x 10(9)/L
• Serum creatinine ≥ 2.5 mg/dL within 14 days before enrollment.
• Patient has \>Grade 2 peripheral neuropathy within 14 days before enrollment.
• 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.
• Patients with a history of treatment for clinically significant ventricular cardiac arrhythmias.
• Patient has hypersensitivity to bortezomib, boron or mannitol.
• Chemotherapy or radiotherapy received within the previous 4 weeks of study enrollment.
• 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.
• Patient has received other investigational drugs with 14 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• 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.
• POEMS Syndrome
• Clinically significant hepatic dysfunction as noted by bilirubin or AST \> 3 times the upper normal limit or clinically significant concurrent hepatitis.
• Uncontrolled, active infection

Sponsors & Collaborators

• University of Arkansas: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms; Hematologic Neoplasms

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; 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; Neoplasms by Site

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Complete data was not received from the primary institution for all six patients enrolled. Data available is represented.

Results Point of Contact

• Title: Maurizio Zangari, MD Principal Investigator
• Organization: Huntsman Cancer Institute at the University of Utah Medical Center

801-585-3229

Study Officials

• Maurizio Zangari, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: February 2, 2010
• First Posted: February 4, 2010
• Study Start: January 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: April 6, 2015
• Results First Posted: April 6, 2015

Record last verified: 2015-04

Locations

US (1)