A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Daratumumab; Bortezomib; Lenalidomide; Dexamethasone; Melphalan; Prednisone; Carfilzomib
Intervention description: Daratumumab will be administered at a dose of 1800 mg by SC injection in Cycles 1 to 4 in D-VRd cohort and until documented progression of disease, unacceptable toxicity, or end of study for D-VMP, D-Rd and D-Kd cohorts.; Bortezomib will be administered as 1.3 mg/m^2 SC injection in Cycles 1 to 4 in D-VRd cohort and in Cycles 1 to 9 in D-VMP cohort.; Lenalidomide will be administered as 25 mg capsule orally in Cycles 1 to 4 in D-VRd cohort and in all Cycles until documented progression of disease, unacceptable toxicity, or end of study in D-Rd cohort.; Dexamethasone will be administered as 20 mg orally or intravenously in Cycles 1 to 4 in D-VRd cohort; 40 mg orally or intravenously in all cycles and thereafter until documented progression of disease, unacceptable toxicity, or end of study in D-Rd and D-Kd cohort.; Melphalan will be administered as 9 mg/m^2 orally in Cycles 1 to 9.; Prednisone will be administered as 60 mg/m^2 orally in cycles 1 to 9.; Carfilzomib will be administered as 20 mg/m^2 IV on Day 1 of Cycle 1 only then 70 mg/m^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or end of study in D-Kd cohort.
Intervention MeSH terms: Dexamethasone; Prednisone; Lenalidomide; Bortezomib; Melphalan; Daratumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 265.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the clinical benefit of subcutaneous (SC)
      daratumumab administered in combination with standard multiple myeloma (MM) regimens in
      participants with MM as measured by overall response rate (ORR) or very good partial response
      (VGPR) or better rate.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG)
             diagnostic criteria

          -  Measurable, secretory disease as defined by any of the following:

               1. Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0
                  gram per deciliter (g/dL); or

               2. Urine M-protein level >= 200 milligram per 24 hours (mg/24 hours); or

               3. Light chain multiple myeloma (MM), for participants without measurable disease in
                  the serum or urine: serum Immunoglobulin (Ig) free light chain (FLC) >= 10 mg/dL
                  and abnormal FLC ratio

          -  Meets one of the sets of the following criteria:

               1. For Daratumumab + bortezomib + lenalidomide + dexamethasone (D-VRd) and
                  Daratumumab + bortezomib + melphalan + prednisone + dexamethasone (D-VMP)
                  regimen: newly diagnosed myeloma

               2. For Daratumumab + lenalidomide + dexamethasone (D-Rd) and Daratumumab +
                  Carfilzomib + Dexamethasone (D-Kd) regimen: relapsed or refractory disease

               3. D-Kd cohort: Participants must have received only 1 prior line of therapy for MM
                  which included at least 2 consecutive cycles of lenalidomide therapy

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0, 1, or 2

          -  During the study, during dose interruptions, and for 3 months after receiving the last
             dose of any component of the study treatment, a female participant must agree not to
             donate eggs (ova, oocytes) and male participants of reproductive potential must not
             donate semen or sperm during the study, during dose interruptions, or for 3 months
             after the last dose of any study drug

        Exclusion Criteria:

          -  History of malignancy (other than MM) unless all treatment of that malignancy was
             completed at least 2 years before consent and the participant has no evidence of
             disease further exceptions are squamous and basal cell carcinomas of the skin and
             carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the
             opinion of the investigator, with concurrence with the sponsor's medical monitor, is
             considered cured with minimal risk of recurrence within 3 years

          -  Exhibits clinical signs of meningeal involvement of MM

          -  Either of the following: a) Chronic obstructive pulmonary disease with a forced
             expiratory volume in 1 second (FEV1) is less than (<) 50 percentage (%) of predicted
             normal b) Moderate or severe persistent asthma, or a history of asthma within the last
             2 years, or currently has uncontrolled asthma of any classification c) For D-Kd
             cohort: Known infiltrative pulmonary disease or known pulmonary hypertension

          -  Any of the following: a) Known to be seropositive for human immunodeficiency virus; b)
             Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
             antigen [HBsAg]). Participants with resolved infection (participants 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 polymerase chain reaction (PCR) positive will be excluded

          -  Known to be seropositive for hepatitis C (Anti-HCV antibody positive or HCV-RNA
             quantitation positive) except in the setting of a sustained virologic response [SVR],
             defined as aviremia at least 12 weeks after completion of antiviral therapy

          -  For D-Kd cohort only: Transthoracic echocardiogram showing left ventricular ejection
             fraction (LVEF) <40%; uncontrolled hypertension, defined as an average systolic blood
             pressure greater than (>)159 millimeters of mercury (mmHg) or diastolic >99 mmHg
             despite optimal treatment