Clinical Trials /

Denosumab for Smoldering Multiple Myeloma

NCT03839459

Description:

This study will assess the safety and tolerability of denosumab in smoldering multiple myeloma subjects as well to see if denosumab can reduce subjects' risk of getting multiple myeloma.

Related Conditions:
  • Smoldering Plasma Cell Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Denosumab for Smoldering Multiple Myeloma
  • Official Title: Denosumab for Smoldering Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: UMMY18121
  • NCT ID: NCT03839459

Conditions

  • Smoldering Multiple Myeloma

Interventions

DrugSynonymsArms
DenosumabDenosumab

Purpose

This study will assess the safety and tolerability of denosumab in smoldering multiple myeloma subjects as well to see if denosumab can reduce subjects' risk of getting multiple myeloma.

Detailed Description

      This is an open label, Phase II trial of denosumab 120mg subcutaneous (SC) for patients with
      smoldering multiple myeloma (SMM). Subjects will be recruited from the James P. Wilmot Cancer
      Center, University of Rochester in Rochester, New York. Patients seen in the inpatient or
      outpatient setting with histologically confirmed SMM will be evaluated for this study.

      20 patients will be treated as follows: Denosumab: day 1 = 120mg SC every 4 weeks for 12
      cycles. Cycles will be 28 days in length. Patients will be followed after completion of the
      study per standard of care for progression free survival for an additional 2 years after the
      last dose of denosumab. All patients will take daily vitamin D and calcium supplements of at
      least 1200mg elemental calcium and 800IU of vitamin D unless documented hypercalcemia
      develops on study. Pre-existing hypocalcemia must be corrected prior to initiating therapy
      with denosumab. Serum vitamin D levels will be checked during screening and should be
      repleted to a total 25-hydroxyvitamin D level ≥30ng/mL.
    

Trial Arms

NameTypeDescriptionInterventions
DenosumabExperimental
  • Denosumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patient has confirmed SMM according to the definition of the International Myeloma
             Working Group (IMWG) definition: serum M-protein ≥3 g/dL or BMPC >10% but less than
             60%, or both, along with normal organ and marrow function (CRAB) within 4 weeks prior
             to baseline. C: Absence of hypercalcemia, evidenced by a calcium ≤11 mg/dL. R: Absence
             of renal failure, evidenced by a creatinine ≤ 2.0mg/dL A: Absence of anemia, evidenced
             by a hemoglobin ≥10 g/dL.

             B: Absence of lytic bone lesions per IMWG recommendations:

             One of either PET-CT, low-dose whole-body CT (LDWBCT) or MRI of the whole body or
             spine. Increased uptake on PET-CT alone is not adequate for the diagnosis of multiple
             myeloma; evidence of underlying osteolytic bone destruction is needed on the CT
             portion of the examination.

          2. One of the risk factors below that portends for an increased risk of progression to
             MM:

               -  An abnormal free light chain ratio

               -  M-spike ≥ 4 g/dL

               -  ≥ 50% bone marrow plasma cells

               -  Immunoparesis ≥ 20% less than the institutional normal standard of the uninvolved
                  immunoglobulins

          3. Serum calcium or albumin-adjusted serum calcium ≥ 2.1 mmol/L (8.4 mg/dL) and ≤
             2.9mmol/L (11.5 mg/dL) (Reference range 8.5-10.8 mg/dL)

          4. Able to tolerate daily supplementation of calcium and vitamin D

          5. Must have a vitamin D level ≥ 30 ng/mL after repletion

          6. Participants must have normal organ as defined below:

               -  Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN); patients
                  diagnosed with Gilbert's syndrome can enroll with a total bilirubin > 2 after
                  review of the principal investigator

               -  AST(SGOT) ≤2.5 × institutional ULN

               -  ALT(SGPT) ≤2.5 × institutional ULN

          7. Age ≥ 18 years.

          8. ECOG PS ≤1

          9. Life expectancy greater than 12 months

         10. Subjects with reproductive potential must be willing to use, in combination with
             his/her partner, 2 highly effective methods of effective contraception or practice
             sexual abstinence throughout the study and continue for 5 months after the study
             duration. Subjects who are surgically sterile (e.g. history of bilateral tubal
             ligation, hysterectomy) or whose sexual partner is sterile (e.g. history of vasectomy)
             are not required to use additional contraceptive measures.

         11. Ability to understand and the willingness to sign a written informed consent document.

             -Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up.

         12. Statement on Inclusion of Women and Minorities - Men and women of all ethnicities and
             racial backgrounds are eligible for this study.

        Exclusion Criteria:

          1. Prior administration of denosumab.

          2. Any history of IV bisphosphonate use prior to or during the study

          3. Prescription oral fluorides or bisphosphonate usage > 3 months within the past 2 years

          4. Systemic corticosteroids > 10mg prednisone per day

          5. Known secondary cause for osteopenia or osteoporosis

          6. Patient has symptomatic MM, as defined by any of the following:

               -  Lytic lesions or pathologic fractures.

               -  Anemia (hemoglobin <10 g/dL)

               -  Hypercalcemia (corrected serum calcium > 11.0 mg/dL)

               -  Renal insufficiency (creatinine > 2.0 mg/dL).

               -  Clonal bone marrow plasma cells > 60%

               -  An involved serum free light chain (kappa or Lambda) > 100mg/L with the ratio of
                  the involved/uninvolved free light chains also > 100 mg/L

               -  One or more osteolytic lesions on radiography, but more than one lesion is
                  required if < 10% marrow plasma cells. From MRI imaging, there must be more than
                  one lesion of > 5mm in size.

          7. Other: symptomatic hyperviscosity, amyloidosis, plasma cell leukemia, POEMS syndrome
             (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein)

          8. Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw.

          9. Active dental or jaw condition that requires oral surgery, including tooth extraction.

         10. Non-healed dental/oral surgery, including tooth extraction.

         11. Planned invasive dental procedures during the course of study.

         12. Evidence of any of the following conditions per subject self-report or medical chart
             review:

               -  Any prior invasive malignancy within 3 years of enrollment that may affect
                  outcome of study

               -  Any non-invasive malignancy not treated with curative intent or with known active
                  disease within 3 years before enrollment that may affect outcome of study

               -  Major surgery or significant traumatic injury occurring within 4 weeks before
                  enrollment

               -  Active infection with Hepatitis B virus or Hepatitis C virus

               -  Known infection with human immunodeficiency virus (HIV) requiring IV
                  anti-infective therapy

         13. Subject is pregnant or breast feeding, or planning to become pregnant within 5 months
             after the end of treatment.

         14. Female subject of child-bearing potential is not willing to use, in combination with
             her partner, 2 methods of highly effective contraception during treatment and for 5
             months after the end of treatment.

         15. Clinically significant hypersensitivity to denosumab or any components of denosumab
             120mg.

         16. Known sensitivity to any of the products to be administered during the study (e.g.,
             calcium, or vitamin D).

         17. Subject is receiving or is less than 14 days since ending other experimental drug (no
             marketing authorization for any indication).

         18. Any major medical or psychiatric disorder that, in the opinion of the investigator,
             might prevent the subject from completing the study or interfere with the
             interpretation of the study results.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of subjects with a downgraded risk of progression of smoldering multiple myeloma if the risk category decreases.
Time Frame:1 year
Safety Issue:
Description:Risk Categories: Low Risk:Patient has SMM, but none of the listed risk factors Low-Intermediate Risk: 1 risk factor is present High-Intermediate Risk: 2 risk factors are present High Risk: 3 risk factors are present Risk Factors: BM plasma cell % ≥50 M-protein ≥ 3g/dL Involved/ un-involved free light chains ≥ 8

Secondary Outcome Measures

Measure:Proportion of subjects with Skeletal related Events
Time Frame:1 year
Safety Issue:
Description:To be determined by the investigator
Measure:Proportion of subjects with disease progression to Multiple Myeloma
Time Frame:1 year
Safety Issue:
Description:Risk Categories: Low Risk:Patient has SMM, but none of the listed risk factors Low-Intermediate Risk: 1 risk factor is present High-Intermediate Risk: 2 risk factors are present High Risk: 3 risk factors are present Risk Factors: BM plasma cell % ≥50 M-protein ≥ 3g/dL Involved/ un-involved free light chains ≥ 8
Measure:Proportion of subjects with progression free survival
Time Frame:3 year
Safety Issue:
Description:time to progression or death from any cause, whichever occurs first.
Measure:Proportion of subjects with change in bone mineral density
Time Frame:1 year
Safety Issue:
Description:baseline and each post-treatment point

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Rochester

Trial Keywords

  • Smoldering Multiple Myeloma
  • Denosumab

Last Updated

April 22, 2019