Clinical Trials /

Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT01665794

Description:

The study will investigate the effects of adding carfilzomib to the combination of pomalidomide and dexamethasone in sequential dose escalation cohorts in patients with relapsed or refractory multiple myeloma. This portion of the study is complete. This study will also investigate the effects of adding daratumumab to the combination of carfilzomib, pomalidomide and dexamethasone.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
  • Official Title: Multicenter, Open-label, Single-arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment With Pomalidomide, Dexamethasone, and Carfilzomib (PdC) in Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 12-1088
  • SECONDARY ID: NCI-2012-01168
  • NCT ID: NCT01665794

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
PomalidomideCC-4047, Pomalyst(R)PdC Group
CarfilzomibKyprolis (R), PR-171PdC Group
dexamethasoneAeroseb-Dex, Decaderm, Decadron, DM, DXMPdC Group
DaratumumabDaralexPdC + Dara Group

Purpose

The study will investigate the effects of adding carfilzomib to the combination of pomalidomide and dexamethasone in sequential dose escalation cohorts in patients with relapsed or refractory multiple myeloma. This portion of the study is complete. This study will also investigate the effects of adding daratumumab to the combination of carfilzomib, pomalidomide and dexamethasone.

Detailed Description

      Patients receive carfilzomib, pomalidomide, and dexamethasone in 28 days treatment cycles.
      Study treatment continues for as long a their myeloma does not worsen and they do not have
      unacceptable side effects. After completion of study treatment, patients are followed for up
      to 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
PdC GroupExperimentalPatients receive carfilzomib, pomalidomide, and dexamethasone at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.
  • Pomalidomide
  • Carfilzomib
  • dexamethasone
PdC + Dara GroupExperimentalPatients receive carfilzomib, pomalidomide, dexamethasone, and daratumumab at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.
  • Pomalidomide
  • Carfilzomib
  • dexamethasone
  • Daratumumab

Eligibility Criteria

        Inclusion Criteria:

          -  Relapsed and relapsed/refractory multiple myeloma requiring systemic therapy

          -  Failed at least one prior treatment for multiple myeloma (must have received
             lenalidomide)

               -  To be enrolled as second line therapy: Must be refractory to lenalidomide
                  (progression on therapy or within 60 days of lenalidomide dosing)

          -  Measurable disease, as indicated by one or more of the following:

               -  Serum M-protein >= 0.5 g/dL

               -  Urine M-protein >= 200 mg/24 hours

               -  If serum protein electrophoresis is felt to be unreliable for routine M-protein
                  measurement, then quantitative immunoglobulin levels are acceptable

               -  Involved serum free light chains ≥ 10 mg/dL (free light change ratio must be
                  abnormal)

          -  Aged 18 years or older

          -  Life expectancy of more than 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Adequate Liver Function

               -  Bilirubin < 1.5 times the upper limit of normal (ULN)

               -  Aspartate aminotransferase (AST) < 2.5 times ULN

               -  Alanine aminotransferase (ALT) < 2.5 times ULN

          -  Absolute neutrophil count (ANC) >= 1.0 x 10^9/L

          -  Hemoglobin >= 8 g/dL

          -  Platelet count >= 75 x 10^9/L (should be independent of platelet transfusions for at
             least 2 weeks)

          -  Calculated or measured creatinine clearance of >= 30 mL/minute

          -  Written informed consent

          -  Negative pregnancy test (for women of childbearing potential) within 10-14 days of
             starting study treatment and again within 24 hours of first pomalidomide dose

          -  Must agree to practice abstinence or use two acceptable methods of birth control

          -  Men must agree to use latex condom during sexual contact with women of childbearing
             potential (even if post vasectomy)

          -  Must agree to adhere to all study requirements, visit schedule, outpatient treatment,
             required concomitant medications, and laboratory monitoring

          -  Must register to mandatory POMALYST REMS™ program and be willing and able to comply
             with the requirements of the POMALYST REMS™ program

        Exclusion Criteria:

          -  Patients for whom there is the prospect of stem cell transplantation in the next 6
             months in the treatment plan are excluded

          -  POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
             skin changes)

          -  Plasma cell leukemia

          -  Waldenström's macroglobulinemia or immunoglobulin M (IgM) myeloma

          -  Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of
             protocol treatment (localized radiotherapy to a single site at least 1 week before
             start is permissible)

          -  Participation in an investigational therapeutic study within 3 weeks or within 5 drug
             half lives (t1/2) prior to first dose, whichever time is greater

          -  Patients known to be refractory to any proteasome inhibitor other than bortezomib or
             carfilzomib

          -  Pregnant or lactating

          -  History of allergy to mannitol or prior hypersensitivity to thalidomide, lenalidomide
             or pomalidomide

          -  Major surgery within 3 weeks prior to first dose,

          -  Prior peripheral stem cell transplant within 12 weeks of study enrollment

          -  Has received any anti-cancer therapy including chemotherapy, immunotherapy,
             radiotherapy, hormonal (with the exception of hormones for thyroid conditions or
             estrogen replacement therapy [ERT]), or any investigational therapy within 21 days of
             enrollment

          -  Myocardial infarction within 6 months prior to enrollment, New York Heart Associate
             (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled
             ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active
             conduction system abnormalities

          -  Uncontrolled hypertension or diabetes

          -  Acute active infection requiring systemic antibiotics, antivirals, or anti fungals
             within two weeks prior to first dose

          -  Known or suspected human immunodeficiency (HIV) infection, known HIV seropositivity

          -  Active hepatitis A, B, or C infection

          -  Non-hematologic malignancy within the past 3 years except adequately treated basal
             cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix or
             breast, prostate cancer < Gleason grade 6 with stable prostate specific antigen levels
             or cancer considered cured by surgical resection alone

          -  Any clinically significant medical disease or condition that, in the investigator's
             opinion, may interfere with protocol adherence or a subject's ability to give informed
             consent

          -  Significant neuropathy (grades 3-4, or grade 2 with pain) at the time of the first
             dose and/or within 14 days before enrollment

          -  Contraindications to any of the required concomitant drugs, including proton-pump
             inhibitor (eg, lansoprazole), enteric-coated aspirin, allopurinol or if a history of
             prior thrombotic disease, warfarin or low molecular weight heparin

          -  Subjects in whom the required program of PO and IV fluid hydration is contraindicated,
             eg, due to pre-existing pulmonary, cardiac, or renal impairment

          -  Subjects with known or suspected amyloidosis of any organ

          -  Subjects with pleural effusions requiring thoracentesis or ascites requiring
             paracentesis

          -  Prior exposure to daratumumab
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of carfilzomib when administered in combination with pomalidomide and dexamethasone
Time Frame:28 days
Safety Issue:
Description:The proportion and exact 95% binomial confidence interval for the response rate will be reported adjusted for the two-stage design of this trial.

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 2 years
Safety Issue:
Description:Defined as at least a partial response to therapy, will be reported along with its exact 95% binomial confidence
Measure:Time to progression
Time Frame:Up to 2 years
Safety Issue:
Description:Estimated using the product-limit method of Kaplan and Meier.
Measure:Duration of response
Time Frame:From the date of the clinical examination which confirmed the response, until the date of disease progression, or censoring at the date of last clinical follow-up up to 2 years
Safety Issue:
Description:Assessed conditional upon achieving at least a partial response.
Measure:Progression-free survival
Time Frame:From the date of first therapy until the date of documented disease progression or death up to 2 years
Safety Issue:
Description:Estimated using the product-limit method of Kaplan and Meier.
Measure:Overall survival
Time Frame:Up to 2 years
Safety Issue:
Description:Estimated using the product-limit method of Kaplan and Meier.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Chicago

Last Updated

April 26, 2019