Clinical Trials /

Global Response Assessment by Advanced Imaging and Myeloma Lesion Biopsies During Induction Therapy of Multiple Myeloma With Carfilzomib Lenalidomide Dexamethasone

NCT03375567

Description:

The primary objective of this study is to compare the detection rate of residual/refractory disease based on standard bone marrow biopsy versus guided myeloma lesion biopsy after induction therapy with carfilzomib, lenalidomide and dexamethasone regimen.

Related Conditions:
  • Extraosseous Plasmacytoma
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Global Response Assessment by Advanced Imaging and Myeloma Lesion Biopsies During Induction Therapy of Multiple Myeloma With Carfilzomib Lenalidomide Dexamethasone
  • Official Title: Global Response Assessment by Advanced Imaging and Myeloma Lesion Biopsies During Induction Therapy of Multiple Myeloma With Carfilzomib Lenalidomide Dexamethasone (CRD)

Clinical Trial IDs

  • ORG STUDY ID: 2000021421
  • NCT ID: NCT03375567

Conditions

  • Multiple Myeloma

Purpose

The primary objective of this study is to compare the detection rate of residual/refractory disease based on standard bone marrow biopsy versus guided myeloma lesion biopsy after induction therapy with carfilzomib, lenalidomide and dexamethasone regimen.

Detailed Description

      Carfilzomib, lenalidomide and dexamethasone (CRD) combination therapy is generally associated
      with high response rates. The expectation is that induction therapy with CRD will result in
      responses within the myeloma lesions. Extrapolating from the published experience on standard
      bone marrow response rates with CRD regimen, it is predicted that guided biopsy of myeloma
      lesions will reveal VGPR/CR/nearCR rate up to 50%. Further, it can be hypothesized that
      myeloma lesion biopsy will increase the detection rate of residual/refractory disease by
      about 20%, as compared with standard bone marrow evaluation. Thus, it is expected that
      myeloma lesion biopsy response rate may be discordant from the standard bone marrow response
      rate. The identification of patients with large residual disease burden in the myeloma
      lesions will indicate the need for further salvage therapy. Based on this, it is expected
      that advanced imaging with guided myeloma lesion biopsy will result in significantly improved
      response assessment strategy after induction therapy, and will allow better selection of
      patients prior to autologous stem cell transplant.
    

Trial Arms

NameTypeDescriptionInterventions
Guided Lesion BiopsiesExperimentalAfter patients are treated with Carfilzomib Lenalidomide Dexamethasone (CRD), lesion biopsies will be performed per usual care. Patients will have biopsies performed on lesions using a novel image guided technique.
    Standard Lesion BiopsiesActive ComparatorAfter patients are treated with Carfilzomib Lenalidomide Dexamethasone (CRD), lesion biopsies will be performed per usual care. Patients will have biopsies performed on lesions using a novel image guided technique.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Patients must be diagnosed with symptomatic multiple myeloma within 90 days prior to
                   registration
      
                -  Patients must have measurable or evaluable disease as defined by having one or more of
                   the following, obtained within 35 days prior to randomization:
      
                -  Detectable monoclonal protein (M-protein) on serum protein electrophoresis
      
                -  Detectable monoclonal protein on a 24 hour urine protein electrophoresis
      
                -  Abnormal serum kappa to lambda free light chain ratio (< 0.26 or > 1.65)
      
                -  Clonal bone marrow plasma cells ≥10%
      
                -  Myeloma-defining bone lesion or extramedullary plasmacytoma on advanced imaging
      
                -  The following laboratory values must be obtained within 35 days prior to registration:
      
                -  Hemoglobin ≥ 7 g/dL
      
                -  Platelet count ≥ 50,000 cells/mm3
      
                -  Absolute neutrophil count ≥ 500 cells/mm3
      
                -  Calculated creatinine clearance ≥ 15 mL/min
      
                -  Bilirubin ≤ 2 mg/dL
      
                -  SGPT (ALT) and SGOT (AST) < 3 times the upper limit of normal. (Red blood cell and
                   platelets transfusion is allowed to maintain the above goal) Patients may have
                   received one cycle (28 days or less) of prior chemotherapy and no more than 320mg of
                   prior dexamethasone (or equivalent dose of prednisone) for treatment of symptomatic
                   myeloma. They may have received lenalidomide, bortezomib, or cyclophosphamide for
                   treatment of symptomatic myeloma. They may not have received prior carfilzomib.
      
                -  Prior radiation therapy to symptomatic lesions is allowed provided 10 days is allowed
                   between the completion of radiation therapy and start of protocol treatment.
      
                -  Prior systemic glucocorticoid use for the treatment of non-malignant disorders is
                   permitted. Prior or concurrent topical or localized glucocorticoid therapy to treat
                   non-malignant comorbid disorders is permitted.
      
                -  Patients must not have active, uncontrolled seizure disorder. Patients must have had
                   no seizures in the last 6 months.
      
                -  Patients must not have uncontrolled concurrent illness including uncontrolled
                   hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled
                   cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would
                   limit compliance with the study.
      
                -  ECOG performance status 0, 1, or 2. (PS 3 allowed if secondary to pain)
      
                -  Patients with monoclonal gammopathy of undetermined significance or asymptomatic
                   multiple myeloma are not eligible.
      
                -  Patients must not have Grade 3 or higher peripheral neuropathy by CTCAE 4.0.
      
                -  Patients must not have active, uncontrolled infection requiring intravenous antibiotic
                   therapy.
      
                -  Patients may have a history of current or previous deep vein thrombosis or pulmonary
                   embolism but must be willing to receive anti-coagulation as prophylaxis if they are
                   not currently on full-dose anticoagulation.
      
                -  Patients must not have New York Heart Association classification III or IV heart
                   failure or myocardial infarction within the previous 6 months and must have left
                   ventricular ejection fraction of at least 40%.
      
                -  Patients with a history of prior malignancy are eligible provided they were treated
                   with curative intent and do not require active therapy (currently treated basal cell,
                   squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
                   are not excluded).
      
                -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
                   test within 14 days prior starting lenalidomide and must either commit to continued
                   abstinence from heterosexual intercourse or begin two acceptable methods of birth
                   control, one highly effective method and one additional effective method at the same
                   time, 14 days before she starts taking lenalidomide. FCBP must also agree to ongoing
                   pregnancy testing. Men must agree to use a latex condom during sexual contact with a
                   FCBP even if they have had a successful vasectomy. All patients must be counseled at a
                   minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
      
                -  The patient must be able to undergo advanced imaging with either WB-MRI or PET scan.
      
                -  The patient must not have any inherited or acquired bleeding diathesis increasing the
                   risk of hemorrhage with guided biopsies.
      
                -  HIV infection is not excluded. Known HIV positive patients must have documented CD4
                   cell count ≥ 350/mm3 and no history of AIDS-related illness.
      
              Exclusion Criteria:
      
                -  Violation of inclusion criteria specifics
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Detection rate of residual/refractory
      Time Frame:4 months
      Safety Issue:
      Description:The purpose of this outcome is to compare standard biopsy procedures with the image guided approach. International Myeloma Working Group (IMWG) Criteria for Response and Progression standards will be used to determine the detection rate of residual/refractory.

      Secondary Outcome Measures

      Measure:Myeloma lesion response rate
      Time Frame:4 months
      Safety Issue:
      Description:International Myeloma Working Group (IMWG) Criteria for Response and Progression standards will be used.
      Measure:Overall clinical response rate
      Time Frame:4 months
      Safety Issue:
      Description:International Myeloma Working Group (IMWG) Criteria for Response and Progression standards will be used.

      Details

      Phase:N/A
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Yale University

      Last Updated

      July 25, 2018