Clinical Trials /

Daratumumab, Carfilzomib, Pomalidomide, Dexamethasone In MM

NCT04176718

Description:

This research study is studying the combination of Carfilzomib and Daratumumab with two standard of care drugs Pomalidomide, and Dexamethasone in people with relapsed and refractory Multiple Myeloma. Relapsed and Refractory Multiple Myeloma is the condition of returned or previous treatment resistant Multiple Myeloma. This research study involves two study drugs and two standard of care drugs. - The names of the study drugs involved in this study are: - Carfilzomib - Daratumumab - The names of the standard of care drugs involved in this study are: - Dexamethasone - Pomalidomide

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Daratumumab, Carfilzomib, Pomalidomide, Dexamethasone In MM
  • Official Title: A Phase II Study of Daratumumab With Weekly Carfilzomib, Pomalidomide, and Dexamethasone in Relapsed and Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 19-379
  • NCT ID: NCT04176718

Conditions

  • Multiple Myeloma
  • Refractory Multiple Myeloma
  • Multiple Myeloma in Relapse
  • Relapse

Interventions

DrugSynonymsArms
DaratumumabDarzalexDaratumumab,Carfilzomib, Pomalidomide and Dexamethasone
CarfilzomibKyprolisDaratumumab,Carfilzomib, Pomalidomide and Dexamethasone
PomalidomidePomalyst, ImnovidDaratumumab,Carfilzomib, Pomalidomide and Dexamethasone
DexamethasoneDexasone, Diodex, hexadrolDaratumumab,Carfilzomib, Pomalidomide and Dexamethasone

Purpose

This research study is studying the combination of Carfilzomib and Daratumumab with two standard of care drugs Pomalidomide, and Dexamethasone in people with relapsed and refractory Multiple Myeloma. Relapsed and Refractory Multiple Myeloma is the condition of returned or previous treatment resistant Multiple Myeloma. This research study involves two study drugs and two standard of care drugs. - The names of the study drugs involved in this study are: - Carfilzomib - Daratumumab - The names of the standard of care drugs involved in this study are: - Dexamethasone - Pomalidomide

Detailed Description

      This phase II, multicenter, open-label study is studying Daratumumab in combination with
      weekly Carfilzomib, Pomalidomide, and Dexamethasone in people with relapsed and refractory
      Multiple Myeloma who have received at least one prior therapy and who have had previous
      treatment with both Lenalidomide and a Proteasome inhibitor.

        -  The research study procedures include screening for eligibility and study treatment
           including evaluations and follow up visits. This research study involves two study drugs
           and two standard of care drugs.

        -  The names of the study drugs involved in this study are:

             -  Carfilzomib

             -  Daratumumab

        -  The names of the standard of care drugs involved in this study are:

             -  Dexamethasone

             -  Pomalidomide

        -  A total of 43 participants will be enrolled to this trial

        -  The U.S. Food and Drug Administration (FDA) has not approved Daratumumab, and
           Carfilzomib for use in treatment of Multiple Myeloma.
    

Trial Arms

NameTypeDescriptionInterventions
Daratumumab,Carfilzomib, Pomalidomide and DexamethasoneExperimentalPatients who meet eligibility criteria for the study will subsequently be enrolled for treatment. Participants will receive daratumumab, carfilzomib, pomalidomide, and dexamethasone on a 28 day schedule. Daratumumab will be given according to cycle and dosage determined by protocol. Carfilzomib will be given 3 times per cycle Pomalidomide will be given daily during cycle. Dexamethasone will be given 8 times per cycle.
  • Daratumumab
  • Carfilzomib
  • Pomalidomide
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Men or women ≥ 18 and ≤ 80 years old

          -  Diagnosis of multiple myeloma:

               -  Serum monoclonal protein ≥ 0.5 g/dL. Patients with IgD disease and lower amounts
                  of monoclonal protein may be permitted to enroll with PI approval

               -  ≥ 200 mg of monoclonal protein in the urine on 24 hour electrophoresis

               -  Serum free light chain ≥ 100 mg/L (10 mg/dL) and abnormal serum free kappa to
                  serum free kappa light chain ratio

          -  Previously treated relapsed and refractory multiple myeloma

               -  Patients must have received at least one prior line of therapy;

               -  Prior therapy must include at least 2 cycles of lenalidomide and at least 2
                  cycles of a proteasome inhibitor (either in separate regimens or within the same
                  regimen)

               -  Disease progression on or within 60 days of completion of last therapy.

          -  ANC ≥ 1000/μL.

               -  G-CSF is not permitted within 14 days of screening.

               -  Patients with ANC <1000/µL can be considered for screening on a case by case
                  basis with additional monitoring, after discussion with and approval from the PI.

          -  Platelet count ≥ 50,000/µL. Platelet transfusion is not permitted within 7 days of
             screening.

          -  Hemoglobin ≥ 8 g/dL. Red blood cell transfusions are permitted to meet eligibility
             criteria.

          -  Calculated creatinine clearance of ≥ 30 mL/min by Cockcroft-Gault equation.

          -  Patient has adequate hepatic function, as evidenced by each of the following:

               -  Serum bilirubin values < 2 mg/dL; and

               -  Serum aspartate transaminase (ALT) and/or aspartate transaminase (AST) values <
                  2.5 × the upper limit of normal (ULN) of the institutional laboratory reference
                  range. Patients with elevated bilirubin due to Gilbert's syndrome may be
                  permitted with PI approval (e.g. total bilirubin <3 mg/dL and normal direct
                  bilirubin).

          -  Must be able to take acetylsalicylic acid (ASA) daily as prophylactic anticoagulation.
             Patients intolerant to ASA may use low molecular weight heparin, apixaban,
             rivaroxaban, or equivalent.

          -  All study participants must be registered into the mandatory Pomalyst REMS program and
             be willing and able to comply with the requirements of the Pomalyst REMS program.

          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
             required in the Pomalyst REMS program.

          -  A man who is sexually active with a woman of childbearing potential and has not had a
             vasectomy must agree to use a barrier method of birth control e.g. either condom with
             spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
             or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men
             must also not donate sperm during the study and for 3 months after receiving the last
             dose of study drug.

          -  Able to swallow capsules whole (pomalidomide capsules cannot be crushed, dissolved or
             broken).

        Exclusion Criteria:

          -  Participants who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to study registration or those who have not
             recovered from adverse events due to agents administered more than 2 weeks earlier.
             Patients may have received dexamethasone within 2 weeks prior to study registration.

          -  Participants who are receiving any other investigational agents.

          -  Last line of therapy with the combination of carfilzomib, pomalidomide, and
             dexamethasone. Note, prior treatment with daratumumab or other anti-CD38 therapy is
             permitted. Prior treatment with carfilzomib or pomalidomide is permitted (as different
             lines of treatment but not in the same combination).

          -  Concomitant high dose corticosteroids. Low dose corticosteroids (maximum dose 10
             mg/day prednisone equivalent) is permitted if given for disorders other than myeloma,
             e.g. adrenal insufficiency, rheumatoid arthritis, etc.

          -  Pregnancy or lactation or planned lactation (breastfeeding).

          -  Prior history of malignancies, other than MM, unless the patient has completed
             definitive treatment and has been free of the disease for ≥ 3 years. Patients who are
             free of disease < 3 years may enroll after discussion with and approval of the PI.
             Exceptions include the following (i.e. the following are eligible to participate):

               -  Basal or squamous cell carcinoma of the skin

               -  Carcinoma in situ of the cervix

               -  Ductal carcinoma in situ of the breast

               -  Incidental histologic finding of prostate cancer (T1a or T1b) managed with
                  surveillance

          -  Patients with plasma cell leukemia, POEMS syndrome, or amyloidosis are excluded from
             this trial.

          -  Seropositive for HIV infection

          -  Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
             antigen [HBsAg]; see exception below). Subjects with resolved infection (ie, subjects
             who are HBsAg negative but positive for antibodies to hepatitis B core antigen
             [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be
             screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B
             virus (HBV) DNA levels. Those who are PCR positive will be excluded. Exception:
             subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as
             the only serologic marker) AND a known history of prior HBV vaccination, do not need
             to be tested for HBV DNA by PCR.

          -  Seropositive for hepatitis C (except in the setting of a sustained virologic response
             [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).

          -  Peripheral neuropathy ≥ grade 2 despite supportive therapy.

          -  Hypersensitivity to daratumumab, thalidomide, lenalidomide, pomalidomide, carfilzomib,
             or dexamethasone (such as Stevens-Johnson syndrome). Rash to immunomodulatory drug
             that can be medically managed is allowable.

          -  Allogeneic stem cell transplant <12 months prior to initiation of study treatment and
             who have not discontinued immunosuppressive treatment for at least four weeks prior to
             initiation of study treatment and who are currently dependent on such treatment.
             Patients may also not have active graft v. host disease (GVHD).

          -  Patient has a history of significant cardiovascular, neurological, endocrine,
             gastrointestinal, respiratory, or inflammatory illness that could preclude study
             participation, pose an undue medical hazard, or interfere with the interpretation of
             the study results, including, but not limited to, patients with congestive heart
             failure (New York Heart Association [NYHA] Class 3 or 4); unstable angina; cardiac
             arrhythmia; recent (within the preceding 6 months) myocardial infarction or stroke;
             hypertension requiring > 2 medications for adequate control; diabetes mellitus with >
             2 episodes of ketoacidosis in the preceding 12 months; or chronic obstructive
             pulmonary disease (COPD) requiring > 2 hospitalizations in the preceding 12 months.

          -  Known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory
             volume [FEV] in 1 second <60% of predicted normal), known moderate or severe
             persistent asthma within 2 years prior to study registration (intermittent asthma is
             allowed). Patient with known or suspected COPD or asthma must have an FEV1 test within
             28 days prior to study registration.

          -  Major surgery within 2 weeks prior to C1D1.

          -  Patient has any other medical, psychiatric, or social condition that would preclude
             participation in the study, pose an undue medical hazard, interfere with the conduct
             of the study, or interfere with interpretation of the study results.

          -  Toxicity from previous anticancer therapy must resolve to baseline levels or to grade
             ≤1, except for alopecia and peripheral neuropathy.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate of the daratumumab, carfilzomib, pomalidomide, and dexamethasone combination
Time Frame:28 Days
Safety Issue:
Description:Simon's two-stage design will be used. An objective response rate of 40%

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:time from randomization to the disease progression or death from any cause up 60 months
Safety Issue:
Description:PFS will be estimated using the Kaplan-Meier method
Measure:Rate of Minimal residual disease (MRD) negative status
Time Frame:112 Days
Safety Issue:
Description:Clonal evolution and clonal heterogeneity will be summarized using descriptive statistics

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Andrew Yee, MD

Trial Keywords

  • Multiple Myeloma
  • Refractory Multiple Myeloma
  • Multiple Myeloma in Relapse
  • Relapse

Last Updated

November 22, 2019