NCT01441973

Biomarker Study of Elotuzumab in High Risk Smoldering Myeloma

Completed Phase 2 Results posted Last updated 23 January 2018

What this trial tests

Phase 2 trial testing Elotuzumab (BMS-901608; HuLuc63) in Smoldering Multiple Myeloma in 41 participants. Completed in 17 January 2017.

Timeline

28 December 2011

Primary endpoint
30 May 2014

17 January 2017

Quick facts

Lead sponsor	Bristol-Myers Squibb
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	41
Start date	28 December 2011
Primary completion	30 May 2014
Estimated completion	17 January 2017
Sites	12 locations across United States

Drugs / interventions tested

• Elotuzumab (BMS-901608; HuLuc63) — full drug profile →

Conditions studied

• Smoldering Multiple Myeloma — all drugs for Smoldering Multiple Myeloma →

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Smoldering Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions Secondary · From day of last patient, first dose to 6 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.

Deaths

Group	Value	95% CI
Elotuzumab, 20 mg/kg	0
Elotuzumab, 10 mg/kg	0
Elotuzumab, All Dosages	0

SAEs

Group	Value	95% CI
Elotuzumab, 20 mg/kg	8
Elotuzumab, 10 mg/kg	7
Elotuzumab, All Dosages	15

AEs leading to discontinuation

Group	Value	95% CI
Elotuzumab, 20 mg/kg	4
Elotuzumab, 10 mg/kg	2
Elotuzumab, All Dosages	6

Infusion reactions

Group	Value	95% CI
Elotuzumab, 20 mg/kg	4
Elotuzumab, 10 mg/kg	1
Elotuzumab, All Dosages	5

Linear Regression of Maximal Percent Reduction in Serum Monoclonal (M) Protein on Baseline Percent CD56^Dim Cells in Bone Marrow Primary · From day of last patient, first dose to 6 months

Estimated using linear regression model, with baseline CD56\^dim cells as the independent covariate, and maximal percent reduction in serum M protein as the dependent variable. For 1 patient who had nonmeasurable disease at baseline, the percent change in serum kappa-lambda difference was used instead of the percent change in serum M protein. Unit of measure=percent change from baseline in M protein cells/ percent change in CD56\^dim cells (% chg from BL in M pro/% chg CD56\^dim cs)

Group	Value	95% CI
Elotuzumab, 20 mg/kg	-2.562	-5.439 – 0.316
Elotuzumab, 10 mg/kg	2.464	0.086 – 4.842
Elotuzumab, All Dosages	0.274	-1.722 – 2.270

Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality Secondary · From date of first dose to date of last dose plus 60 days (assessed up to August 2017, approximately 59 months

Clinical laboratory evaluations included hematology, chemistry, and liver and renal functioning.

Lymphocytes

Group	Value	95% CI
Elotuzumab, 20 mg/kg	2
Elotuzumab, 10 mg/kg	1
Elotuzumab, All Dosages	3

Hyponatremia

Group	Value	95% CI
Elotuzumab, 20 mg/kg	1
Elotuzumab, 10 mg/kg	1
Elotuzumab, All Dosages	2

Hyperkalemia

Group	Value	95% CI
Elotuzumab, 20 mg/kg	0
Elotuzumab, 10 mg/kg	1
Elotuzumab, All Dosages	1

Hyperglycemia

Group	Value	95% CI
Elotuzumab, 20 mg/kg	1
Elotuzumab, 10 mg/kg	2
Elotuzumab, All Dosages	3

Number of Participants With a Dose- or Concentration-related Effect on QTcF Interval, PR Interval, QRS Interval, and Heart Rate Secondary · cycle 1 to first day of cycle 3 assessed up to 08/17, approximately 59 months

All on-treatment electrocardiograms (ECGs) were performed in triplicates ( 1 ECG test equaled 3 consecutive individual 12-lead ECGs performed within a 4-minute period). The timing of the ECG was critical to the endpoint of the study. The investigative site documented any deviations from the protocol or procedures related to ECG collection or serum sampling. No ECGs were excluded due to timing deviations; no deviations were considered clinically relevant and all ECG data were included.

Group	Value	95% CI
Elotuzumab, 20 mg/kg	0
Elotuzumab, 10 mg/kg	0
Elotuzumab, All Dosages	0

Progression Free Survival (PFS) Rate Secondary · Up to 2 years from the initiation of study therapy by dose cohort (approximately 24 months)

The probability was estimated from the K-M curve of subjects being alive and without disease progression (modified IMWG criteria) at 2 years from the initiation of study therapy by dose cohort

Group	Value	95% CI
Elotuzumab, 20 mg/kg	0.71	0.45 – 0.86
Elotuzumab, 10 mg/kg	0.54	0.31 – 0.72
Elotuzumab, All Dosages	0.62	0.45 – 0.75

Objective Response Rate (ORR) Secondary · From first dose to date of progression or objective response (assessed up to August 2017, approximately 59 months)

ORR is defined as the number of participants with stringent compete response \[SCR\], complete response \[CR\], very good partial response \[VGPR\], and partial response \[PR\])/number of participants in arm, expressed as a percentage. Confidence intervals computed using the Clopper and Pearson method. SCR=CR plus normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR=Negative immunofixation on serum and urine and 5% or fewer plasma cells in bone marrow. VGPR=Serum and urine monoclonal (M) protein detectable by immunofixation

Group	Value	95% CI
Elotuzumab, 20 mg/kg	13.3	2.4 – 36.3
Elotuzumab, 10 mg/kg	6.3	0.3 – 26.4
Elotuzumab, All Dosages	9.7	2.7 – 23.2

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Elotuzumab(E) : 10 mg/kg/Dose

Serious: 7/16 (44%)

Deaths: —

Elotuzumab(E) : 20 mg/kg/Dose

Serious: 8/15 (53%)

Deaths: —

Serious adverse events (20 terms)

Reaction	System	Elotuzumab(E) : 10 mg/kg/D…	Elotuzumab(E) : 20 mg/kg/D…
Vertigo	Ear and labyrinth disorders	—	—
Asthenia	General disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Arthritis bacterial	Infections and infestations	—	—
Influenza	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Rectal abscess	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Urosepsis	Infections and infestations	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Pathological fracture	Musculoskeletal and connective tissue disorders	—	—
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Transient ischaemic attack	Nervous system disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (246 terms — click to expand)

Reaction	System	Elotuzumab(E) : 10 mg/kg/D…	Elotuzumab(E) : 20 mg/kg/D…
Upper respiratory tract infection	Infections and infestations	—	—
Fatigue	General disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Headache	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Rhinitis	Infections and infestations	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—
Chills	General disorders	—	—
Oedema peripheral	General disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Paraesthesia	Nervous system disorders	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—
Wheezing	Respiratory, thoracic and mediastinal disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Malaise	General disorders	—	—
Herpes zoster	Infections and infestations	—	—
Oral candidiasis	Infections and infestations	—	—
Sinusitis	Infections and infestations	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—
Neuropathy peripheral	Nervous system disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Increased tendency to bruise	Blood and lymphatic system disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Cerumen impaction	Ear and labyrinth disorders	—	—
Eye irritation	Eye disorders	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—
Abdominal distension	Gastrointestinal disorders	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Tooth disorder	Gastrointestinal disorders	—	—

Most-reported serious reactions: Vertigo, Asthenia, Non-cardiac chest pain, Arthritis bacterial, Influenza, Pneumonia, Rectal abscess, Upper respiratory tract infection.

Data from ClinicalTrials.gov NCT01441973 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether elotuzumab will improve response in patients with high risk smoldering myeloma who have more CD56\^dim cells (a marker for the health of the body's immune system)

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Monoclonal antibodies in the treatment of multiple myeloma: current status and future perspectives.
   Lonial S, Durie B, Palumbo A, San-Miguel J. · · 2016 · cited 67× · PMID 26265184 · DOI 10.1038/leu.2015.223
2. A look backward and forward in the regulatory and treatment history of multiple myeloma: Approval of novel-novel agents, new drug development, and longer patient survival.
   Kazandjian D, Landgren O. · · 2016 · cited 53× · PMID 28061986 · DOI 10.1053/j.seminoncol.2016.10.008
3. Pursuing a Curative Approach in Multiple Myeloma: A Review of New Therapeutic Strategies.
   D'Agostino M, Bertamini L, Oliva S, Boccadoro M, et al · · 2019 · cited 32× · PMID 31847174 · DOI 10.3390/cancers11122015
4. Elotuzumab monotherapy in patients with smouldering multiple myeloma: a phase 2 study.
   Jagannath S, Laubach J, Wong E, Stockerl-Goldstein K, et al · · 2018 · cited 30× · PMID 29808907 · DOI 10.1111/bjh.15384
5. 2021 European Myeloma Network review and consensus statement on smoldering multiple myeloma: how to distinguish (and manage) Dr. Jekyll and Mr. Hyde.
   Musto P, Engelhardt M, Caers J, Bolli N, et al · · 2021 · cited 29× · PMID 34261295 · DOI 10.3324/haematol.2021.278519
6. Profile of elotuzumab and its potential in the treatment of multiple myeloma.
   Liu YC, Szmania S, van Rhee F. · · 2014 · cited 24× · PMID 26005365 · DOI 10.2147/blctt.s49780
7. Treatment of multiple myeloma with the immunostimulatory SLAMF7 antibody elotuzumab.
   Einsele H, Schreder M. · · 2016 · cited 16× · PMID 27695618 · DOI 10.1177/2040620716657993
8. Dilemmas in treating smoldering multiple myeloma.
   Ahn IE, Mailankody S, Korde N, Landgren O. · · 2015 · cited 14× · PMID 25422486 · DOI 10.1200/jco.2014.56.4351