Clinical Trials /

Role of Osteocytes in Myeloma Bone Disease

NCT02212262

Description:

Progress in the treatment of myeloma and myeloma bone disease has substantially increased overall survival, but relapse is inevitable and better treatment is needed. The bone microenvironment is tremendously complex, so that targeting single interactions between tumor and bone is unlikely to be effective. Treatments need to block centrally important, multifunctional pathways. The investigators data point to a central role of the osteocyte to induce heparanase, a multifunctional mediator of myeloma bone disease. Increased heparanase due to FGF23 may make systemic inhibitors of heparanase less effective in bone than elsewhere. FGF23 neutralizing antibodies have been developed for non-cancer conditions of FGF23 excess, such as chronic kidney disease (Shimada & Fukamoto, 2012), and could be used in MM alone or in combination with heparanase inhibitors. Complete neutralization of FGF23 has adverse effects, but neutralization of FGF23 excess may be practical, or in the future, suppression of excess FGF23 biosynthesis by osteocytes. The investigators hope to determine serum FGF23 and heparanase, Dkk1 and plasma klotho levels in patients with newly diagnosed and relapsed myeloma compared to healthy controls with this exploratory study.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

URL:

https://clinicaltrials.gov/show/NCT02212262

Trial Eligibility

Document

Title

  • Brief Title: Role of Osteocytes in Myeloma Bone Disease
  • Official Title: Role of Osteocytes in Myeloma Bone Disease

Clinical Trial IDs

  • ORG STUDY ID: IUCRO-0498
  • NCT ID: NCT02212262

Conditions

  • Multiple Myeloma

Purpose

Progress in the treatment of myeloma and myeloma bone disease has substantially increased overall survival, but relapse is inevitable and better treatment is needed. The bone microenvironment is tremendously complex, so that targeting single interactions between tumor and bone is unlikely to be effective. Treatments need to block centrally important, multifunctional pathways. The investigators data point to a central role of the osteocyte to induce heparanase, a multifunctional mediator of myeloma bone disease. Increased heparanase due to FGF23 may make systemic inhibitors of heparanase less effective in bone than elsewhere. FGF23 neutralizing antibodies have been developed for non-cancer conditions of FGF23 excess, such as chronic kidney disease (Shimada & Fukamoto, 2012), and could be used in MM alone or in combination with heparanase inhibitors. Complete neutralization of FGF23 has adverse effects, but neutralization of FGF23 excess may be practical, or in the future, suppression of excess FGF23 biosynthesis by osteocytes. The investigators hope to determine serum FGF23 and heparanase, Dkk1 and plasma klotho levels in patients with newly diagnosed and relapsed myeloma compared to healthy controls with this exploratory study.

Trial Arms

NameTypeDescriptionInterventions
Multiple Myeloma PatientsPatients with multiple myeloma will undergo a blood draw and a bone marrow aspirate. Extra bone marrow will be taken for study purposes only.
    Healthy subjectsHealthy subjects and multiple myeloma patients will undergo a blood draw

      Eligibility Criteria

              Inclusion Criteria:

          1. Age > 18 years but ≤ 95 years at the time of consent

          2. Subjects must be English-speaking

          3. Must voluntarily sign the most current informed consent and HIPAA documents prior to
             study participation.

          4. Have no prior history of malignancy in the past 5 years with the exception of basal
             cell and squamous cell carcinoma of the skin. Other cancers with low potential for
             metastasis, such as in situ cancers can also be enrolled as healthy volunteers.

          5. Have no known liver or kidney disorders

        Exclusion Criteria:

          1. Pregnant females will be excluded from the study.

          2. Subjects allergic to xylocaine will be excluded.

          3. Subjects with an acute illness (Ex. upper respiratory infection, viral illness) in the
             past seven days will be excluded.

          4. History of bleeding disorders.

          5. Subjects deemed incompetent by treating physician

          6. Institutionalized, mentally disabled subjects

          7. Subjects who are prisoners
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:Accepts Healthy Volunteers

      Primary Outcome Measures

      Measure:Molecular interactions between multiple myeloma and osteocytes
      Time Frame:Up to 4 years
      Safety Issue:
      Description:To determine FGF23 and heparanase, Dkk1 and plasma klotho levels increase in patients with newly diagnosed and relapsed myeloma compared to healthy controls.

      Secondary Outcome Measures

      Measure:Multiple Myeloma osteocytes and tumor staging
      Time Frame:Up to 4 years
      Safety Issue:
      Description:To correlate the FGF23, heparanase, Dkk1 and plasma klotho to tumor staging
      Measure:Multiple Myeloma osteocytes and Type I collagen fragments on bone resorption
      Time Frame:Up to 4 years
      Safety Issue:
      Description:To correlate the FGF23, heparanase, Dkk1 and plasma klotho to extent of bone resorption using serum type I collagen fragments ICTP and CTX

      Details

      Phase:
      Primary Purpose:Observational
      Overall Status:Recruiting
      Lead Sponsor:Attaya Suvannasankha

      Last Updated

      September 29, 2020