Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma.
Condition: Relapsed Multiple Myeloma; Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Dexamethasone; Daratumumab; Carfilzomib
Intervention description: Commercially available oral and IV formulas were obtained by investigative sites. Amgen supplied IV or PO dexa for some countries (Poland, Hungry, Romania, Bulgaria, Korea). Dosage modification rules applied based on participant age (participants > 75 years were given lower doses), dexa-related toxicities, and discontinuation of carfilzomib.; Daratumumab was supplied as a concentrated solution for infusion in single-use vials.; Carfilzomib for infusion was supplied as a lyophilized, sterile product in single-use vials. The lyophilized product was reconstituted with preservative-free sterile water for injection, the reconstituted solution contained carfilzomib 2 mg/mL. IV injections lasted approximately 30 minutes.
Dose could be modified based on a >20% change in body weight or toxicity.
Intervention MeSH terms: Dexamethasone; Daratumumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 466.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Carfilzomib; Dexamethasone; Daratumumab

Summary:

      Compare carfizomib, dexamethasone, and daratumumab (KdD) to Carfilzomib and dexamethasone
      (Kd) in terms of progression free survival (PFS) in participants with multiple myeloma who
      have relapsed after 1 to 3 prior therapies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Criteria 1 Relapsed or progressive multiple myeloma after last treatment

          -  Criteria 2 Males or females ≥ 18 years of age

          -  Criteria 3 Measurable disease with at least 1 of the following assessed within 21 days
             prior to randomization:

          -  IgG multiple myeloma: serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL,

          -  IgA, IgD, IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL,

          -  urine M-protein ≥ 200 mg/24 hours,

          -  in subjects without measurable serum or urine M- protein, serum free light chain
             (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio

          -  Criteria 4 Received at least 1 but not more than 3 prior lines of therapy for multiple
             myeloma (induction therapy followed by stem cell transplant and
             consolidation/maintenance therapy will be considered as 1 line of therapy

          -  Criteria 5 Prior therapy with carfilzomib is allowed as long as the patient had at
             least a partial response (PR) to most recent therapy with carfilzomib, was not removed
             due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib,
             and will have at least a 6-month carfilzomib treatment-free interval from last dose
             received until first study treatment. (Patients may receive maintenance therapy with
             drugs that are not proteasome inhibitors or CD38 antibodies during this 6-month
             carfilzomib treatment free interval)

          -  Criteria 6 Prior therapy with anti-CD38 antibodies is allowed as long as the patient
             had at least a PR to most recent therapy with CD38 antibody, was not removed due to
             toxicity, did not relapse within 60 days from intensive treatment (at least every
             other week) of CD38 antibody therapy, and will have at least a 6 month CD38 antibody
             treatment-free interval from last dose received until first study treatment

          -  Other inclusion criteria may apply

        Exclusion Criteria:

          -  Criteria 1 Waldenström macroglobulinemia

          -  Criteria 2 Multiple myeloma of IgM subtype

          -  Criteria 3 POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal
             protein, and skin changes)

          -  Criteria 4 Plasma cell leukemia (> 2.0 * 10^9/L circulating plasma cells by standard
             differential)

          -  Criteria 5 Myelodysplastic syndrome

          -  Criteria 6 Known moderate or severe persistent asthma within the past 2 years

          -  Criteria 7 Known chronic obstructive pulmonary disease (COPD) with a FEV1 < 50% of
             predicted normal

          -  Criteria 8 Active congestive heart failure (New York Heart Association [NYHA] Class
             III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant
             electrocardiogram (ECG) abnormalities, screening ECG with corrected QT interval (QTc)
             of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to
             randomization

          -  Other exclusion criteria may apply