Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability of Elotuzumab when given in combination with Lenalidomide and low-dose Dexamethasone in subjects with relapsed or refractory multiple myeloma (MM) in Japan.
Interventions
BIOLOGICALBMS-901608 (Elotuzumab) 10 mg
Injection, Intravenous, 10 mg/kg, Weekly at cycle 1 and 2, bi-weekly at cycle 3 and thereafter, Until disease progression or unacceptable toxicity became apparent
BIOLOGICALBMS-901608 (Elotuzumab) 20 mg
Injection, Intravenous, 20 mg/kg, Weekly at cycle 1 and 2, bi-weekly at cycle 3 and thereafter, Until disease progression or unacceptable toxicity became apparent
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email MyCancerStudyConnect@emergingmed.com. Please visit www.BMSStudyConnect.com for more information on clinical trial participation. Inclusion Criteria: * Received between 1 to 4 prior lines of therapy * Measureable disease * Men and women of childbearing potential (WOCBP) must be using two acceptable methods of contraception * Men must agree to use a latex condom and a second form of birth control during sexual contact with WOCBP and must agree to not donate semen during study drug therapy * Subjects must be willing to refrain from blood donations during study drug therapy
Exclusion criteria
* Subjects with non-secretory or oligo-secretory or light-chain only myeloma or active/prior plasma cell leukemia or known /suspect POEMS syndrome * Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia * Unable to take aspirin daily as prophylactic anticoagulation therapy. Prior history of inability to tolerate weekly 40 mg dexamethasone * History of renal failure * History of clinical significant thrombosis, such as treatment for thrombosis was required
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months) | NCI CTCAE, version 3.0 was used to measure toxicity scale. Sodium high (H) Gr 1:\>ULN - 150; Gr 2: \>150 - 155; Gr 3: \>155 - 160; Gr 4: \>160 mmol/L; Sodium low(L) Gr 1:\<LLN - 130; Gr 3: \<130 - 120; Gr 4: \<120 mmol/L. Potassium (H) Gr 1: \>ULN - 5.5; Gr 2: \>5.5 - 6.0; Gr 3: \> 6.0 - 7.0; Gr 4: \>7.0 mmol/L; Potassium (L) Gr 1 - Gr 2: \<LLN - 3.0; Gr 3: \< 3.0 - 2.5; Gr 4: \<2.5 mmol/L. |
| Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months) | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Data cut-off February 2014. |
| Number of Participants With Clinically Relevant Vital Sign Findings | First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months) | Vital signs (body temperature, seated blood pressure, heart rate, and respiration rate) were recorded at screening on Days 1, 8, 15, and 22 of Cycles 1 and 2, on Days 1 and 15 of Cycle 3, and at the end of treatment. Blood pressure (Diastolic and Systolic) and heart rate were recorded after the participant sat quietly for at least 5 minutes. Clinical relevance of vital sign data was determined by the investigator. |
| Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months) | National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. Lymphocytes (absolute) Gr 1: \<1.5 to 0.8 \*10\^3 c/µL, Gr 2 \<0.8 to 0.5 \*10\^3 c/µL, Gr 3: \<0.5 to 0.2 \*10\^3 c/µL, Gr 4: \<0.2\*10\^3 c/µL. Neutrophils (absolute): Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L. Platelet count Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L. Leukocytes Gr 1:\<LLN to 3.0 \*10\^3 c/µL, Gr 2; \<3.0 to 2.0 \*10\^3 c/µL, Gr 3: \<2.0 to 1.0 \*10\^3 c/µL, Gr 4: \<1.0 \*10\^3 c/µL. |
| Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months) | National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:\>1.0 to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. AST Gr 1: \>1.0 to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Total bilirubin Gr 1: \>1.0 to 1.5\*ULN; Gr 2: \>1.5 to 3.0\*ULN; Gr 3: \>3.0 to 10..0\*ULN; Gr 4: \>10.0.0\*ULN. ALP (U/L) Gr1:\>1.0 to 2.5\*ULN, Gr2:\>2.5 to 5.0\*ULN, Gr3:\>5.0 to 20.0\*ULN, Gr4:\>20.0\*ULN. Albumin (low) Gr 1:\<LLN to 3 grams per deciliter (g/dL); Gr 2: \<3.0 - 2.0 g/L; Gr 3: \< 2 g/dL. Creatinine Gr 1: \>1 - 1.5\*baseline (BL)to \>ULN - 1.5\*ULN; Gr 2: \>1.5 - 3.0\*BL to \> 1.5 - 3.0\*ULN; Gr 3: \>3.0\*BL to \> 3.0 - 6.0\*ULN; Gr 4: \>6.0\*ULN. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Days 1, 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3 | The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h. |
| Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Days 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3 | The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmin was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h. |
| Number of Participants Positive for Anti-Elotuzumab Anti-drug Antibodies - Treated Participants | First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months) | The detection of anti-elotuzumab anti-drug antibodies (ADAs) in human serum was performed using a validated bridging electrochemiluminescence immunoassay (ECLA) on the Meso Scale Discovery (MSD) platform. Sample collection was performed prior to administration of elotuzumab at Day 1 of each cycle. |
| Number of Participants With Best Overall Response - Treated Participants | Cycle 2 (Study Day 29) to last dose (assessed up to January 2017, approximately 71 months) | Complete response (CR) and Partial Response (PR) were based on the European Group for Blood and Bone Marrow Transplant (EBMT) Criteria. Very Good Partial response was derived from the International Myeloma Working Group (IMWG) criteria. Participants who had a reduction in M-protein or plasmacytoma but did not meet the EBMT criteria for PR were classified as minimal response (MR). Hematologic, radiologic and/or clinical assessments were done every cycle starting with cycle 2. Each cycle is 4 weeks in length (Day 1, Day 8, Day 15, Day 22). Cycle 2 began on study Day 29. CR=negative immunofixation 6 weeks, \<5% plasma cells, no increase in size or number of lytic lesions, complete disappearance of extramedullary plasmacytoma. PR=≥50%reduction in M-protein for 6 weeks, ≥90% reduction of urinary light chain excretion or \< 200 mg/24hours for 6 weeks, ≥50% reduction in size of extramedullary plasmacytoma present at baseline, no increase in size or number of lytic lesions. |
Countries
Japan
Participant flow
Pre-assignment details
Seven participants were enrolled and 6 entered the treatment period. Reason for 1 participant not entering treatment period: participant no longer met study criteria.
Participants by arm
| Arm | Count |
|---|---|
| Elotuzumab 10 mg/kg Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion). | 3 |
| Elotuzumab 20 mg/kg Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion). | 3 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Reason by Sponsor | 1 | 0 |
| Overall Study | Disease Progression | 2 | 0 |
| Overall Study | Participant Discontinued Treatment | 0 | 2 |
| Overall Study | Study Drug Toxicity | 0 | 1 |
Baseline characteristics
| Characteristic | Elotuzumab 20 mg/kg | Total | Elotuzumab 10 mg/kg |
|---|---|---|---|
| Age, Continuous | 66.0 years | 63.5 years | 61.0 years |
| Age, Customized 65 to < 75 | 1 participants | 2 participants | 1 participants |
| Age, Customized Greater than, equal to 75 | 1 participants | 1 participants | 0 participants |
| Age, Customized Less than (<) 65 | 1 participants | 3 participants | 2 participants |
| Region of Enrollment Japan | 3 participants | 6 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 | 3 / 3 |
Outcome results
Primary
Number of Participants With Clinically Relevant Vital Sign Findings
Vital signs (body temperature, seated blood pressure, heart rate, and respiration rate) were recorded at screening on Days 1, 8, 15, and 22 of Cycles 1 and 2, on Days 1 and 15 of Cycle 3, and at the end of treatment. Blood pressure (Diastolic and Systolic) and heart rate were recorded after the participant sat quietly for at least 5 minutes. Clinical relevance of vital sign data was determined by the investigator.
Time frame: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Population: All participants who received at least one dose of study medication were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elotuzumab 10 mg/kg | Number of Participants With Clinically Relevant Vital Sign Findings | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Clinically Relevant Vital Sign Findings | 0 participants |
Primary
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Data cut-off February 2014.
Time frame: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Population: All participants who received at least one dose of study medication were summarized (Treated Participants).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab 10 mg/kg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | Grade 3-4 SAEs | 1 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | Grade 3-4 AEs | 3 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | AEs Leading to Discontinuation | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | Deaths | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | All SAEs Any Grade | 2 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | Deaths | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | All SAEs Any Grade | 3 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | Grade 3-4 SAEs | 3 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | AEs Leading to Discontinuation | 1 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths | Grade 3-4 AEs | 3 participants |
Primary
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests
NCI CTCAE, version 3.0 was used to measure toxicity scale. Sodium high (H) Gr 1:\>ULN - 150; Gr 2: \>150 - 155; Gr 3: \>155 - 160; Gr 4: \>160 mmol/L; Sodium low(L) Gr 1:\<LLN - 130; Gr 3: \<130 - 120; Gr 4: \<120 mmol/L. Potassium (H) Gr 1: \>ULN - 5.5; Gr 2: \>5.5 - 6.0; Gr 3: \> 6.0 - 7.0; Gr 4: \>7.0 mmol/L; Potassium (L) Gr 1 - Gr 2: \<LLN - 3.0; Gr 3: \< 3.0 - 2.5; Gr 4: \<2.5 mmol/L.
Time frame: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Population: All participants who received at least one dose of study medication were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium High, Any Grade | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium High, Grade 3-4 | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium Low, Any Grade | 3 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium Low, Grade 3-4 | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium High, Any Grade | 1 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium High, Grade 3-4 | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium Low, Any Grade | 2 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium Low, Grade 3-4 | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium Low, Grade 3-4 | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium High, Any Grade | 2 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium High, Any Grade | 2 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium High, Grade 3-4 | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium Low, Any Grade | 3 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium Low, Any Grade | 2 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Sodium High, Grade 3-4 | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests | Potassium Low, Grade 3-4 | 1 participants |
Primary
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. Lymphocytes (absolute) Gr 1: \<1.5 to 0.8 \*10\^3 c/µL, Gr 2 \<0.8 to 0.5 \*10\^3 c/µL, Gr 3: \<0.5 to 0.2 \*10\^3 c/µL, Gr 4: \<0.2\*10\^3 c/µL. Neutrophils (absolute): Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L. Platelet count Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L. Leukocytes Gr 1:\<LLN to 3.0 \*10\^3 c/µL, Gr 2; \<3.0 to 2.0 \*10\^3 c/µL, Gr 3: \<2.0 to 1.0 \*10\^3 c/µL, Gr 4: \<1.0 \*10\^3 c/µL.
Time frame: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Population: All participants who received at least one dose of study medication were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Hemoglobin Any Grade | 3 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Hemoglobin Grade 3-4 | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Lymphocytes Any Grade | 3 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Lymphocytes Grade 3-4 | 3 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Neutrophils Any Grade | 3 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Neutrophils Grade 3-4 | 2 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Platelet Count Any Grade | 3 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Platelet Count Grade 3-4 | 1 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Leukocytes Any Grade | 3 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Leukocytes Grade 3-4 | 2 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Platelet Count Grade 3-4 | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Hemoglobin Any Grade | 3 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Neutrophils Grade 3-4 | 3 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Hemoglobin Grade 3-4 | 1 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Leukocytes Grade 3-4 | 1 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Lymphocytes Any Grade | 3 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Platelet Count Any Grade | 2 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Lymphocytes Grade 3-4 | 3 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Leukocytes Any Grade | 3 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests | Neutrophils Any Grade | 3 participants |
Primary
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:\>1.0 to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. AST Gr 1: \>1.0 to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Total bilirubin Gr 1: \>1.0 to 1.5\*ULN; Gr 2: \>1.5 to 3.0\*ULN; Gr 3: \>3.0 to 10..0\*ULN; Gr 4: \>10.0.0\*ULN. ALP (U/L) Gr1:\>1.0 to 2.5\*ULN, Gr2:\>2.5 to 5.0\*ULN, Gr3:\>5.0 to 20.0\*ULN, Gr4:\>20.0\*ULN. Albumin (low) Gr 1:\<LLN to 3 grams per deciliter (g/dL); Gr 2: \<3.0 - 2.0 g/L; Gr 3: \< 2 g/dL. Creatinine Gr 1: \>1 - 1.5\*baseline (BL)to \>ULN - 1.5\*ULN; Gr 2: \>1.5 - 3.0\*BL to \> 1.5 - 3.0\*ULN; Gr 3: \>3.0\*BL to \> 3.0 - 6.0\*ULN; Gr 4: \>6.0\*ULN.
Time frame: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Population: All participants who received at least one dose of study medication were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Albumin Any Grade | 3 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Albumin Grade 3-4 | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALP Any Grade | 1 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALP Grade 3-4 | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALT Any Grade | 2 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALT Grade 3-4 | 1 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | AST Any Grade | 1 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | AST Grade 3-4 | 1 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Creatinine Any Grade | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Creatinine Grade 3-4 | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Bilirubin Total Any Grade | 1 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Bilirubin Total Grade 3-4 | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Bilirubin Total Any Grade | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Albumin Any Grade | 3 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | AST Any Grade | 2 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Albumin Grade 3-4 | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Creatinine Grade 3-4 | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALP Any Grade | 2 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | AST Grade 3-4 | 1 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALP Grade 3-4 | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Bilirubin Total Grade 3-4 | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALT Any Grade | 2 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | Creatinine Any Grade | 2 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests | ALT Grade 3-4 | 1 participants |
Secondary
Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3
The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h.
Time frame: Days 1, 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3
Population: All participants who received at least one dose of study medication and had adequate Pharmacokinetic (PK) concentration profiles were summarized.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Elotuzumab 10 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 1 Day 15 (n=3,3) | 297 µg/mL | Geometric Coefficient of Variation 10 |
| Elotuzumab 10 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 2 Day 1 (n=3,3) | 240 µg/mL | Geometric Coefficient of Variation 28 |
| Elotuzumab 10 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 1 Day 8 (n=3,3) | 237 µg/mL | Geometric Coefficient of Variation 19 |
| Elotuzumab 10 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 2 Day 22 (n=3,3) | 270 µg/mL | Geometric Coefficient of Variation 32 |
| Elotuzumab 10 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 1 Day 22 (n=3,2) | 234 µg/mL | Geometric Coefficient of Variation 14 |
| Elotuzumab 10 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 3 Day 1 (n=3,3) | 286 µg/mL | Geometric Coefficient of Variation 32 |
| Elotuzumab 10 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 1 Day 1 (n=3,3) | 173 µg/mL | Geometric Coefficient of Variation 9 |
| Elotuzumab 20 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 3 Day 1 (n=3,3) | 972 µg/mL | Geometric Coefficient of Variation 32 |
| Elotuzumab 20 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 1 Day 1 (n=3,3) | 376 µg/mL | Geometric Coefficient of Variation 14 |
| Elotuzumab 20 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 1 Day 8 (n=3,3) | 549 µg/mL | Geometric Coefficient of Variation 18 |
| Elotuzumab 20 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 1 Day 15 (n=3,3) | 652 µg/mL | Geometric Coefficient of Variation 21 |
| Elotuzumab 20 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 1 Day 22 (n=3,2) | 724 µg/mL | Geometric Coefficient of Variation 45 |
| Elotuzumab 20 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 2 Day 1 (n=3,3) | 671 µg/mL | Geometric Coefficient of Variation 51 |
| Elotuzumab 20 mg/kg | Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 | Cycle 2 Day 22 (n=3,3) | 844 µg/mL | Geometric Coefficient of Variation 26 |
Secondary
Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3
The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmin was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h.
Time frame: Days 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3
Population: All participants who received at least one dose of study medication and had adequate PK concentration profiles were summarized.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Elotuzumab 10 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 1 Day 22 (n=3,2) | 24.6 µg/mL | Geometric Coefficient of Variation 87 |
| Elotuzumab 10 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 2 Day 22 (n=3,3) | 57.8 µg/mL | Geometric Coefficient of Variation 82 |
| Elotuzumab 10 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 1 Day 15 (n=3,3) | 97.0 µg/mL | Geometric Coefficient of Variation 12 |
| Elotuzumab 10 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 3 Day 1 (n=3,3) | 77.2 µg/mL | Geometric Coefficient of Variation 78 |
| Elotuzumab 10 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 2 Day 1 (n=3,2) | 25.8 µg/mL | Geometric Coefficient of Variation 95 |
| Elotuzumab 10 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 3 Day 15 (n=3,3) | 59.4 µg/mL | Geometric Coefficient of Variation 78 |
| Elotuzumab 10 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 1 Day 8 (n=3,3) | 59.1 µg/mL | Geometric Coefficient of Variation 28 |
| Elotuzumab 20 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 3 Day 15 (n=3,3) | 466 µg/mL | Geometric Coefficient of Variation 38 |
| Elotuzumab 20 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 1 Day 8 (n=3,3) | 165 µg/mL | Geometric Coefficient of Variation 20 |
| Elotuzumab 20 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 1 Day 15 (n=3,3) | 252 µg/mL | Geometric Coefficient of Variation 30 |
| Elotuzumab 20 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 1 Day 22 (n=3,2) | 280 µg/mL | Geometric Coefficient of Variation 62 |
| Elotuzumab 20 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 2 Day 1 (n=3,2) | 389 µg/mL | Geometric Coefficient of Variation 64 |
| Elotuzumab 20 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 2 Day 22 (n=3,3) | 547 µg/mL | Geometric Coefficient of Variation 41 |
| Elotuzumab 20 mg/kg | Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 | Cycle 3 Day 1 (n=3,3) | 579 µg/mL | Geometric Coefficient of Variation 46 |
Secondary
Number of Participants Positive for Anti-Elotuzumab Anti-drug Antibodies - Treated Participants
The detection of anti-elotuzumab anti-drug antibodies (ADAs) in human serum was performed using a validated bridging electrochemiluminescence immunoassay (ECLA) on the Meso Scale Discovery (MSD) platform. Sample collection was performed prior to administration of elotuzumab at Day 1 of each cycle.
Time frame: First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Population: All participants who received at least one dose of study medication were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elotuzumab 10 mg/kg | Number of Participants Positive for Anti-Elotuzumab Anti-drug Antibodies - Treated Participants | 3 participants |
| Elotuzumab 20 mg/kg | Number of Participants Positive for Anti-Elotuzumab Anti-drug Antibodies - Treated Participants | 0 participants |
Secondary
Number of Participants With Best Overall Response - Treated Participants
Complete response (CR) and Partial Response (PR) were based on the European Group for Blood and Bone Marrow Transplant (EBMT) Criteria. Very Good Partial response was derived from the International Myeloma Working Group (IMWG) criteria. Participants who had a reduction in M-protein or plasmacytoma but did not meet the EBMT criteria for PR were classified as minimal response (MR). Hematologic, radiologic and/or clinical assessments were done every cycle starting with cycle 2. Each cycle is 4 weeks in length (Day 1, Day 8, Day 15, Day 22). Cycle 2 began on study Day 29. CR=negative immunofixation 6 weeks, \<5% plasma cells, no increase in size or number of lytic lesions, complete disappearance of extramedullary plasmacytoma. PR=≥50%reduction in M-protein for 6 weeks, ≥90% reduction of urinary light chain excretion or \< 200 mg/24hours for 6 weeks, ≥50% reduction in size of extramedullary plasmacytoma present at baseline, no increase in size or number of lytic lesions.
Time frame: Cycle 2 (Study Day 29) to last dose (assessed up to January 2017, approximately 71 months)
Population: All participants who received at least one dose of study medication were summarized (Treated Participants).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab 10 mg/kg | Number of Participants With Best Overall Response - Treated Participants | Complete Response | 0 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Best Overall Response - Treated Participants | Very Good Partial Response | 1 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Best Overall Response - Treated Participants | Partial Response | 1 participants |
| Elotuzumab 10 mg/kg | Number of Participants With Best Overall Response - Treated Participants | Minimal Response | 1 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Best Overall Response - Treated Participants | Minimal Response | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Best Overall Response - Treated Participants | Complete Response | 1 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Best Overall Response - Treated Participants | Partial Response | 0 participants |
| Elotuzumab 20 mg/kg | Number of Participants With Best Overall Response - Treated Participants | Very Good Partial Response | 2 participants |