Clinical Trials /

Daratumumab, Carfilzomib, Lenalidomide and Low Dose Dexamethasone (DKRd) in Newly Diagnosed, Multiple Myeloma

NCT03500445

Description:

The purpose of this study is to determine response rate after 8 cycles of D-KRd (daratumumab, carfilzomib, lenalidomide (Revlimid) and dexamethasone in patients with multiple myeloma.

Related Conditions:
  • Multiple Myeloma
  • Plasmacytoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Daratumumab, Carfilzomib, Lenalidomide and Low Dose Dexamethasone (DKRd) in Newly Diagnosed, Multiple Myeloma
  • Official Title: Open-label, Single-arm, Phase 2 Study of Initial Treatment With Daratumumab (Darzalex), Carfilzomib (Kyprolis), Lenalidomide (Revlimid) and Low Dose Dexamethasone (DKRd) in Newly Diagnosed, Multiple Myeloma Requiring Systemic Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: IRB17-1097
  • NCT ID: NCT03500445

Conditions

  • Myeloma
  • Multiple Myeloma

Interventions

DrugSynonymsArms
DaratumumabDARZALEX®Treatment Arm (D-KRd)
CarfilzomibKYPROLIS®Treatment Arm (D-KRd)
LenalidomideREVLIMID®Treatment Arm (D-KRd)
DexamethasoneTreatment Arm (D-KRd)

Purpose

The purpose of this study is to determine response rate after 8 cycles of D-KRd (daratumumab, carfilzomib, lenalidomide (Revlimid) and dexamethasone in patients with multiple myeloma.

Trial Arms

NameTypeDescriptionInterventions
Treatment Arm (D-KRd)Experimental
  • Daratumumab
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy

             • Prior treatment of hypercalcemia or spinal cord compression or active and/or
             aggressively progressing myeloma with corticosteroids or lenalidomide or
             bortezomib-based regimens does not disqualify the patient (the treatment dose should
             not exceed the equivalent of 160 mg of dexamethasone in a 4 week period or not more
             than 1 cycle of Proteasome Inhibitor / Immunomodulatory-based therapy)

          -  Both transplant and non-transplant candidates are eligible.

          -  Diagnosis of symptomatic multiple myeloma as per current International Myeloma Working
             Group (IMWG) uniform criteria prior to initial treatment

          -  Monoclonal plasma cells in the Bone Marrow (BM) ≥ 10% or presence of a biopsy-proven
             plasmacytoma

          -  Measurable disease, prior to initial treatment as indicated by one or more of the
             following:

               -  Serum M-protein ≥ 1 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

               -  Serum freelite measurable disease as per current IMWG criteria

          -  Bone marrow specimen will be required at study entry; available DNA sample from
             pre-induction BM will be used for calibration step for MRD evaluation by gene
             sequencing.

          -  Males and females ≥ 18 years of age

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Adequate hepatic function, with bilirubin ≤ 1.5 x upper limit of normal (ULN) and
             aspirate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN

          -  Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 8 g/dL, platelet count ≥
             75 x 109/L.

          -  Calculated creatinine clearance (by Cockroft-Gault) ≥ 50 mL/min or serum creatinine
             below 2 g/dL

          -  Woman of childbearing potential must have 2 negative pregnancy tests prior to
             initiating lenalidomide.

          -  Woman of childbearing potential must agree to use 2 reliable forms of contraception
             simultaneously or to practice complete abstinence from heterosexual intercourse during
             the following time periods related to this study: 1) for at least 28 days before
             starting lenalidomide; 2) while participating in the study; and 3) for at least 30
             days after discontinuation from the study.

          -  Male subjects must agree to use a latex condom during sexual contact with females of
             childbearing potential while participating in the study and for at least 90 days
             following discontinuation from the study even if he has undergone a successful
             vasectomy.

          -  All study participants in the US must be consented to and registered into the
             mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS®) program and be
             willing and able to comply with the requirements of Revlimid REMS®.

          -  Voluntary written informed consent.

        Exclusion Criteria:

          -  Frail non-transplant candidates, defined as in Palumbo et al, Blood 2015.

          -  Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as
             <1.0 g/dL M-protein in serum, <200 mg/24 hr urine M-protein, and no measurable disease
             as per IMWG by Freelite.

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

          -  Amyloidosis

          -  Plasma cell leukemia

          -  Waldenström's macroglobulinemia or Immunoglobulin M-producing (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

          -  Potential subjects with evidence of progressive disease as per IMWG criteria

          -  Patients not able to tolerate daratumumab, carfilzomib, lenalidomide or dexamethasone

          -  Peripheral neuropathy ≥ Grade 2 at screening

          -  Diarrhea > Grade 1 in the absence of antidiarrheals

          -  Central Nervous System (CNS) involvement

          -  Pregnant or lactating females

          -  Major surgery within 3 weeks prior to first dose.

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

          -  Prior or concurrent pulmonary embolism

          -  Known moderate or severe persistent asthma or known chronic obstructive pulmonary
             disease (COPD)

               -  Known or suspected chronic obstructive pulmonary disease (COPD) with a forced
                  expiratory volume in 1 second (FEV1) <50% of predicted normal

               -  Moderate or severe persistent asthma within the past 2 years, or currently has
                  uncontrolled asthma of any classification. Note that subjects who currently have
                  controlled intermittent asthma or controlled mild persistent asthma are allowed
                  in the study.

          -  Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG
             during screening

          -  Uncontrolled hypertension or diabetes

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

          -  Known seropositive for or active viral infection with human immunodeficiency virus
             (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are
             seropositive because of hepatitis B virus vaccine are eligible.

          -  Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3
             years except a) adequately treated basal cell, squamous cell skin cancer, thyroid
             cancer, carcinoma in situ of the cervix, or 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of stringent complete response (sCR)
Time Frame:8 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Long term rate of MRD-negative disease
Time Frame:2 years
Safety Issue:
Description:
Measure:Duration of response
Time Frame:1 year
Safety Issue:
Description:
Measure:Rate of progression free survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Time to progression
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall survival rate
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall response rate
Time Frame:2 years
Safety Issue:
Description:
Measure:Number of grade 2 or higher side effects as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria
Time Frame:8 months
Safety Issue:
Description:

Details

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

Last Updated

October 7, 2019