Effect of Low Dose Bortezomib on Bone Formation in Smoldering Myeloma Patients
Condition: Cancer; Myeloma; Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma
Intervention: Bortezomib
Intervention description: Bortezomib will be administered as a 3-5 second bolus IV injection at the dose of 0.7 mg/m2 on days 1, 8, 15, and 22 of each 42 day cycle.
Patients will undergo nine 42-day cycles. At the end of this (day 378), patients will be assessed for bone remodeling changes. Evaluation for toxicities will be evaluated at the beginning of each cycle.
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cancer; myeloma; multiple myeloma; smoldering myeloma

Summary:

      OBJECTIVES

        -  Primary: To evaluate the bone anabolic effect of bortezomib in patients with smoldering
           myeloma.

        -  Secondary: To evaluate the effect of bortezomib on the natural history of smoldering
           myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with diagnosis of smoldering multiple myeloma

          -  Male or Female patients aged ≥ 18 years old

          -  Ability to provide written informed consent (obtained prior to participation in the
             study and any related procedures being performed) 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             may be withdrawn by the subject at any time without prejudice to future medical care.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

          -  Male subject agrees to use an acceptable method for contraception for the duration of
             the study.

          -  Serum M protein ≥3 g/dL and/or

          -  Bone marrow plasma cells ≥10%

          -  Absence of anemia, renal failure, hypercalcemia, and lytic bone lesions

          -  ANC ≥ 1.5 x 109 /L

          -  Hemoglobin ≥ 10g/dl

          -  Platelets ≥ 100 x 109 /L

          -  AST and ALT ≤2.5 x ULN

          -  Serum bilirubin ≤2.0 x ULN

        Exclusion Criteria:

          -  Platelet count of <100 109/L within 14 days before enrollment.

          -  Absolute neutrophil count of <1.0 109/L within 14 days before enrollment.

          -  Creatinine clearance of <30 mL/minute 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 8.4), 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.

          -  Patient has hypersensitivity to bortezomib, boron or mannitol.

          -  Female subject is pregnant or breast-feeding. Confirmation that the subject is not
             pregnant must be established by a negative serum human chorionic gonadotropin (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.

          -  Patients currently taking bisphosphonates