Clinical Trials /

Dexamethasone, Elotuzumab, and Pomalidomide in Treating Patients With Refractory Multiple Myeloma

NCT03713294

Description:

This phase II trial studies how well dexamethasone, elotuzumab, pomalidomide work in treating patients with multiple myeloma that has not responded to previous treatment. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as elotuzumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pomalidomide may stop the growth of multiple myeloma by blocking the growth of new blood vessels necessary for tumor growth. Giving dexamethasone, elotuzumab, pomalidomide may work better in treating patients with multiple myeloma.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dexamethasone, Elotuzumab, and Pomalidomide in Treating Patients With Refractory Multiple Myeloma
  • Official Title: Phase II Trial of Sequential Treatment of Multiple Myeloma With Antibody Therapy

Clinical Trial IDs

  • ORG STUDY ID: MC1884
  • SECONDARY ID: NCI-2018-02140
  • SECONDARY ID: MC1884
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03713294

Conditions

  • Refractory Plasma Cell Myeloma

Interventions

DrugSynonymsArms
DexamethasoneAacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, VisumetazoneTreatment (dexamethasone, elotuzumab, pomalidomide)
ElotuzumabBMS-901608, Empliciti, HuLuc-63, HuLuc63, PDL-063, PDL063Treatment (dexamethasone, elotuzumab, pomalidomide)
Pomalidomide4-Aminothalidomide, Actimid, CC-4047, Imnovid, PomalystTreatment (dexamethasone, elotuzumab, pomalidomide)

Purpose

This phase II trial studies how well dexamethasone, elotuzumab, pomalidomide work in treating patients with multiple myeloma that has not responded to previous treatment. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as elotuzumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pomalidomide may stop the growth of multiple myeloma by blocking the growth of new blood vessels necessary for tumor growth. Giving dexamethasone, elotuzumab, pomalidomide may work better in treating patients with multiple myeloma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the overall response rate (ORR) of utilizing elotuzumab, pomalidomide and
      dexamethasone in patients with disease refractory to daratumumab.

      SECONDARY OBJECTIVES:

      I. To determine percentage of patients achieving complete response (CR) with the elotuzumab
      combination.

      II. To determine progression-free survival (PFS) for treatment with the elotuzumab
      combination.

      III. To determine safety profile for treatment with the elotuzumab combination. IV. To
      determine the overall survival (OS) for patients receiving treatment with the elotuzumab
      combination.

      OUTLINE:

      Patients receive dexamethasone intravenously (IV) on days 1, 8, 15, and 22 of courses 1-2 and
      IV on day 1 and orally (PO) on days 8, 15, and 22 of subsequent courses and elotuzumab IV on
      days 1, 8, 15, and 22 of courses 1-2 and day 1 of subsequent courses. Patients also receive
      pomalidomide PO on days 1-21. Courses repeat every 28 days in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months until
      progressive disease, then every 6 months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (dexamethasone, elotuzumab, pomalidomide)ExperimentalPatients receive dexamethasone IV on days 1, 8, 15, and 22 of courses 1-2 and IV on day 1 and orally (PO) on days 8, 15, and 22 of subsequent courses and elotuzumab IV on days 1, 8, 15, and 22 of courses 1-2 and day 1 of subsequent courses. Patients also receive pomalidomide PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Dexamethasone
  • Elotuzumab
  • Pomalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically confirmed diagnosis of multiple myeloma and noted to have progressive
             disease (International Myeloma Working Group [IMWG] criteria).

          -  At least one prior line of therapy.

          -  Disease refractory to daratumumab as defined by disease progression while on or =< 60
             days of completing treatment with a daratumumab-containing regimen as part of any
             prior line of therapy.

          -  Measurable disease =< 14 days prior to registration.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2.

          -  Absolute neutrophil count (ANC) >= 1,000 cell/mm^3 without growth factor support
             (obtained =< 14 days prior to registration).

          -  Platelet >= 50,000 cells/mm^3 for patients who have bone marrow plasmacytosis < 50% or
             >= 30,000 cells/mm^3 for patients who have bone marrow plasmacytosis of >= 50%
             (obtained =< 14 days prior to registration).

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert?s syndrome,
             in which case the direct bilirubin must be =< 1.5 x ULN (obtained =< 14 days prior to
             registration).

          -  Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (obtained
             =< 14 days prior to registration).

          -  Prothrombin time (PT)/international normalized ratio (INR)/activated partial
             thromboplastin time (aPTT) =< 1.5 x ULN OR if patient is receiving anticoagulant
             therapy and PT/INR or aPTT is within target range of therapy (obtained =< 14 days
             prior to registration).

          -  Calculated or measured creatinine clearance >= 30 ml/min (obtained =< 14 days prior to
             registration).

          -  Negative urine or serum pregnancy test done =< 14 days prior to registration, for
             persons of childbearing potential only.

               -  NOTE: If the urine test is positive or cannot be confirmed as negative, a serum
                  pregnancy test will be required.

          -  Provide written informed consent.

          -  Willing to return to enrolling institution for follow-up (during the Active Monitoring
             Phase of the study).

          -  Willing to follow the requirements of the (Revlimid/Pomalyst) Risk Evaluation and
             Mitigation Strategies (REMS) program.

        Exclusion Criteria:

          -  Non-secretory multiple myeloma (MM) or known immunoglobulin light chain (AL)
             amyloidosis.

          -  Clinically significant active infection requiring intravenous antibiotics (=< 14 days
             prior to registration).

          -  >= Grade 3 neuropathy and/or POEMS syndrome (plasma cell dyscrasia with
             polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).

          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
             positive and currently receiving antiretroviral therapy.

               -  NOTE: Patients known to be HIV positive, but without clinical evidence of an
                  immunocompromised state, are eligible for this trial.

          -  Concurrent therapy considered investigational.

               -  NOTE: Patients must not be planning to receive any radiation therapy (except
                  localized radiation for palliative care that must be completed prior to starting
                  Cycle 1, Day 1).

          -  Any of the following because this study involves an investigational agent whose
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
             unknown:

               -  Pregnant women.

               -  Nursing women (lactating females are eligible provided that they agree not to
                  breast feed while taking lenalidomide).

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception.

          -  Other active malignancy =< 3 years prior to registration.

               -  EXCEPTIONS:

                    -  Adequately treated basal cell or squamous cell skin cancer.

                    -  Any in situ cancer.

                    -  Adequately treated Stage I or II cancer from which the patient is currently
                       in complete remission, or

               -  NOTE: If there is a history of prior malignancy, they must not be receiving other
                  specific treatment for their cancer.

          -  Major surgery =< 4 weeks prior to registration.

          -  History of stroke/intracranial hemorrhage =< 6 months prior to registration.

          -  Clinically significant cardiac illness including New York Heart Association (NYHA)
             Class III or Class IV heart failure, unstable angina pectoris, myocardial infarction
             within the past 6 months, or >= Grade 3 cardiac arrhythmias noted =< 14 days prior to
             registration.

          -  Currently active, clinically significant hepatic impairment Child-Pugh class B or C
             according to the Child Pugh classification.

          -  Exhibiting clinical signs of meningeal involvement of multiple myeloma.

          -  Known severe chronic obstructive pulmonary disease or asthma defined as forced
             expiratory volume (FEV1) in 1 second < 60% of expected.

          -  Prior exposure to elotuzumab.

          -  Prior history of disease refractory to pomalidomide.

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens.

          -  Uncontrolled intercurrent illness including, but not limited to:

               -  Ongoing or active infection.

               -  Symptomatic congestive heart failure.

               -  Unstable angina pectoris.

               -  Cardiac arrhythmia.

               -  Or psychiatric illness/social situations that would limit compliance with study
                  requirements.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR) defined as a partial response, very good partial response, complete response (CR) or stringent CR (sCR)
Time Frame:Up to 5 years
Safety Issue:
Description:The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Secondary Outcome Measures

Measure:Percentage of patients achieving complete response (CR)
Time Frame:Up to 5 years
Safety Issue:
Description:Will be estimated by the number of patients who achieve a sCR or CR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true complete response rate will be calculated.
Measure:Progression-free survival (PFS)
Time Frame:From time of registration to time of progression or death due to any cause assessed up to 5 years
Safety Issue:
Description:The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
Measure:Incidence of adverse events
Time Frame:Up to 5 years
Safety Issue:
Description:The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.
Measure:Overall survival (OS)
Time Frame:Time from registration to death due to any cause assessed up to 5 years
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Trial Keywords

  • multiple myeloma

Last Updated

January 29, 2020