Clinical Trials /

A Study of Daratumumab in Patients With Newly Diagnosed Multiple Myeloma

NCT03290950

Description:

This is a study to test the safety and effectiveness of the study drug, daratumumab in combination with carfilzomib, lenalidomide and dexamethasone. The purpose of this study is to test whether giving daratumumab along with the other drugs (carfilzomib, lenalidomide and dexamethasone) is safe for patients.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Daratumumab in Patients With Newly Diagnosed Multiple Myeloma
  • Official Title: Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Newly-Diagnosed Multiple Myeloma: A Clinical and Correlative Phase II Study

Clinical Trial IDs

  • ORG STUDY ID: 17-352
  • NCT ID: NCT03290950

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
daratumumabCohort 1
carfilzomibCohort 1
lenalidomideCohort 1
dexamethasoneCohort 1 administrationCohort 1
dexamethasoneCohort 2 administrationCohort 2

Purpose

This is a study to test the safety and effectiveness of the study drug, daratumumab in combination with carfilzomib, lenalidomide and dexamethasone. The purpose of this study is to test whether giving daratumumab along with the other drugs (carfilzomib, lenalidomide and dexamethasone) is safe for patients.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalSingle arm, two-stage phase II trial of combination therapy (daratumumab, carfilzomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma patients.
  • daratumumab
  • carfilzomib
  • lenalidomide
  • dexamethasone
Cohort 2ExperimentalSingle arm, two-stage phase II trial of combination therapy (daratumumab, carfilzomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma patients.
  • daratumumab
  • carfilzomib
  • lenalidomide
  • dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Newly diagnosed patients with histologically confirmed MM based on the following
             criteria:

               -  Clonal plasma cells in the bone marrow

               -  Measurable disease within the past 4 weeks defined by any one of the following:

               -  Serum monoclonal protein ≥ 1.0 g/dL

               -  Urine monoclonal protein >200 mg/24 hour

               -  Involved serum immunoglobulin free light chain > 10 mg/dL AND abnormal
                  kappa/lambda ratio

          -  Evidence of underlying end organ damage and/or myeloma defining event attributed to
             underlying plasma cell proliferative disorder meeting at least one of the following:

               -  Hypercalcemia: serum calcium >0.25 mmol/L (> 1 mg/dL) above upper limit of normal
                  or ≥ 2.75 mmol/L (11 mg/dL)

               -  Anemia: hemoglobin value <10 g/dL or > 2 g/dL below lower limit of normal

               -  Bone disease: ≥ 1 lytic lesions on skeletal X-ray, CT, or PET-CT. For patients
                  with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal plasma cells

               -  Clonal bone marrow plasma cell percentage ≥60%

               -  Involved/un-involved serum free light chain ratio ≥100 and involved free light
                  chain >100 mg/L.

                    -  1 focal lesion on magnetic resonance imaging study (lesion must be >5 mm) in
                       size

          -  Creatinine Clearance ≥ 60 ml/min. CrCl can be measured or estimated using
             Cockcroft-Gault method, MDRD, or CKD-EPI formulae

          -  Age ≥ 18 years at the time of signing the informed consent documentation

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Absolute neutrophil
             count (ANC) ≥ 1.0 K/uL, hemoglobin ≥ 8 g/dL, and platelet count ≥ 75 K/uL, unless if
             cytopenias are deemed to be due disease at discretion of clinical investigator.
             Transfusions and growth factors are permissible.

          -  Adequate hepatic function, with bilirubin < 1.5 x the ULN, and AST and ALT < 3.0 x
             ULN.

          -  All study participants must be able to tolerate one of the following
             thromboprophylactic strategies: aspirin, low molecular weight heparin or warfarin
             (coumadin) or alternative anti-coagulant.

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

          -  Females of childbearing potential (FCBP)† must have a negative serum or urine
             pregnancy test within 10 - 14 days and again within 24 hours prior to prescribing
             lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) 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, at least 28 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.

               -  A female of childbearing potential is a sexually mature female who: 1) has not
                  undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
                  postmenopausal for at least 24 consecutive months (i.e., has had menses at any
                  time in the preceding 24 consecutive months).

        Exclusion Criteria:

          -  Patients receiving >1 cycle of prior treatment or concurrent systemic treatment for
             multiple myeloma

               -  Treatment of hypercalcemia or spinal cord compression or aggressively progressing
                  myeloma with current or prior corticosteroids is permitted

               -  Bisphosphonates are permitted

               -  Concurrent or prior treatment with corticosteroids for indications other than
                  multiple myeloma is permitted

               -  Prior treatment with radiotherapy is permitted

               -  Prior treatment for smoldering myeloma is permitted with a washout period of 2
                  weeks from last dose. Smoldering patients previously treated with carfilzomib are
                  excluded.

               -  Patients with measurable disease who received up to one cycle of any therapy
                  within 60 days with a washout period of 2 weeks from last dose (on a trial or
                  outside a trial) are eligible

          -  Plasma cell leukemia

          -  POEMS syndrome

          -  Amyloidosis

          -  Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1
             second (FEV1) <50% of predicted normal (note that FEV1 testing is required for
             subjects suspected of having chronic obstructive pulmonary disease and subjects must
             be excluded if FEV1 <50% of predicted normal).

          -  Pregnant or lactating females. Because there is a potential risk for adverse events
             nursing infants secondary to treatment of the mother with carfilzomib in combination
             with lenalidomide. These potential risks may also apply to other agents used in this
             study.

          -  Uncontrolled hypertension or diabetes

          -  Active hepatitis B or C infection

          -  Subject is:

               -  Seropositive for human immunodeficiency virus (HIV)

               -  Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
                  antigen [HBsAg]). Subjects with resolved infection (i.e., 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).

          -  Has significant cardiovascular disease with NYHA Class III or IV symptoms, EF<40% or
             hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction
             within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as
             determined by history and physical examination. Echocardiogram will be performed
             during screening evaluation.

          -  Pulmonary hypertension

          -  Has refractory GI disease with refractory nausea/vomiting, inflammatory bowel disease,
             or bowel resection that would prevent absorption of oral agents

          -  Uncontrolled intercurrent illness including but not limited to active infection or
             psychiatric illness/social situations that would compromise compliance with study
             requirements

          -  Significant neuropathy ≥Grade 3 or Grade 2 neuropathy with pain at baseline

          -  Contraindication to any concomitant medication, including antivirals or
             anticoagulation.

          -  Major surgery within 3 weeks prior to first dose
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:assess the rate of MRD negativity
Time Frame:2 years
Safety Issue:
Description:Patients with ≤ PR after completing 4 cycles will be included in the analysis of the primary objective and will be considered MRD positive. Patients who receive any study drug and have at least one post-baseline disease assessment will be considered evaluable for the primary endpoint.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Daratumumab
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
  • 17-352

Last Updated

November 6, 2019