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Lenalidomide/Bortezomib/Dexamethasone & CNTO 328 in Transplant Eligible Newly Diagnosed Multiple Myeloma (MM)

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ClinicalTrials.gov Identifier: NCT01531998
Recruitment Status : Completed
First Posted : February 13, 2012
Results First Posted : June 19, 2015
Last Update Posted : June 19, 2015
Sponsor:
Collaborator:
Janssen Services, LLC
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Myeloma
Interventions Drug: Lenalidomide
Drug: Bortezomib
Drug: Siltuximab
Drug: Dexamethasone
Behavioral: Questionnaires
Enrollment 14
Recruitment Details Recruitment Period: May 10, 2012 to February 08, 2013. All recruitment done at The University of Texas MD Anderson Cancer Center.
Pre-assignment Details Of the fourteen participant enrolled, three were screen failures and not enrolled on the study.
Arm/Group Title Siltuximab + Bortezomib + Lenalidomide
Hide Arm/Group Description Induction of Lenalidomide 25 mg orally Days 1-14; Bortezomib 1.3 mg/m^2 intravenous Days 1, 4, 8 and 11; Dexamethasone 20 mg orally Days 1, 2, 4, 5, 8, 9, 11, 12. Siltuximab 11 mg/kg intravenous Day 1. If delayed transplant, induction therapy continued up to 2 cycles beyond achieving a CR/nCR then transition to maintenance therapy (Lenalidomide at last tolerated dose Day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg). Siltuximab 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy. Bortezomib at last tolerated dose Day 1 and Day 8 Dexamethasone at last tolerated dose or 20 mg weekly.
Period Title: Overall Study
Started 11
Completed 8
Not Completed 3
Reason Not Completed
Withdrawal by Subject             3
Arm/Group Title Siltuximab + Bortezomib + Lenalidomide
Hide Arm/Group Description Induction of Lenalidomide 25 mg orally Days 1-14; Bortezomib 1.3 mg/m^2 intravenous Days 1, 4, 8 and 11; Dexamethasone 20 mg orally Days 1, 2, 4, 5, 8, 9, 11, 12. Siltuximab 11 mg/kg intravenous Day 1. If delayed transplant, induction therapy continued up to 2 cycles beyond achieving a CR/nCR then transition to maintenance therapy (Lenalidomide at last tolerated dose Day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg). Siltuximab 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy. Bortezomib at last tolerated dose Day 1 and Day 8 Dexamethasone at last tolerated dose or 20 mg weekly.
Overall Number of Baseline Participants 11
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 11 participants
62
(47 to 73)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Female
7
  63.6%
Male
4
  36.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 11 participants
11
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) of Siltuximab
Hide Description Maximum tolerated dose (MTD) defined as follows: At first dose level, if greater than 1 out of 3 patients or greater than 1 out of 6 patients experience dose limiting toxicity (DLT), the dose level exceeds the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) defined as toxicities graded in severity according to the guidelines outlined in the NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
Time Frame 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Siltuximab + Bortezomib + Lenalidomide
Hide Arm/Group Description:
Induction of Lenalidomide 25 mg orally Days 1-14; Bortezomib 1.3 mg/m^2 intravenous Days 1, 4, 8 and 11; Dexamethasone 20 mg orally Days 1, 2, 4, 5, 8, 9, 11, 12. Siltuximab 11 mg/kg intravenous Day 1. If delayed transplant, induction therapy continued up to 2 cycles beyond achieving a CR/nCR then transition to maintenance therapy (Lenalidomide at last tolerated dose Day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg). Siltuximab 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy. Bortezomib at last tolerated dose Day 1 and Day 8 Dexamethasone at last tolerated dose or 20 mg weekly.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: mg/kg
8.3
2.Secondary Outcome
Title Number of Participants With Response
Hide Description Overall response defined as number of participants with International Myeloma Working Group Uniform Response Criteria: Complete Response (CR): Negative immunofixation serum & urine, Disappearance soft tissue plasmacytomas & =/<5% plasma cells in bone marrow; Stringent Complete Remission: CR + Normal Normal free light chain (FLC) ratio & Absence clonal cells in bone marrow by Immunohistochemistry/ immunofluorescence; Very Good Partial Response (VGPR): Serum & urine M-protein detectable by immunofixation but not on electrophoresis or 90%> reduction in serum M-protein +urine M-protein level <100mg per 24 hour; Partial Remission (PR): =/>50% reduction serum M-protein & reduction in 24-hour urinaryMprotein by >90% or to < 200mg per 24 hour, =/>50% reduction of serum M-protein & reduction in 24-hour urinary Mprotein by >90%/or <200mg, and if present at baseline, a >50% reduction in size of soft tissue plasmacytomas; Stable Disease: Not CR, VGPR, PR Or Progressive disease
Time Frame Evaluated after eight cycles of 21 days.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Siltuximab + Bortezomib + Lenalidomide
Hide Arm/Group Description:
Induction of Lenalidomide 25 mg orally Days 1-14; Bortezomib 1.3 mg/m^2 intravenous Days 1, 4, 8 and 11; Dexamethasone 20 mg orally Days 1, 2, 4, 5, 8, 9, 11, 12. Siltuximab 11 mg/kg intravenous Day 1. If delayed transplant, induction therapy continued up to 2 cycles beyond achieving a CR/nCR then transition to maintenance therapy (Lenalidomide at last tolerated dose Day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg). Siltuximab 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy. Bortezomib at last tolerated dose Day 1 and Day 8 Dexamethasone at last tolerated dose or 20 mg weekly.
Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: participants
Complete Remission (CR) 2
Stringent Complete Remission 0
Very good partial remission (VGPR) 2
Partial Remission (PR) 6
Stable Disease 0
Time Frame Adverse event collection during the first cycle of 28-day study drug administration. Overall collection period: May 2012 to February 2013.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Siltuximab + Bortezomib + Lenalidomide
Hide Arm/Group Description Induction of Lenalidomide 25 mg orally Days 1-14; Bortezomib 1.3 mg/m^2 intravenous Days 1, 4, 8 and 11; Dexamethasone 20 mg orally Days 1, 2, 4, 5, 8, 9, 11, 12. Siltuximab 11 mg/kg intravenous Day 1. If delayed transplant, induction therapy continued up to 2 cycles beyond achieving a CR/nCR then transition to maintenance therapy (Lenalidomide at last tolerated dose Day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg). Siltuximab 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy. Bortezomib at last tolerated dose Day 1 and Day 8 Dexamethasone at last tolerated dose or 20 mg weekly.
All-Cause Mortality
Siltuximab + Bortezomib + Lenalidomide
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Siltuximab + Bortezomib + Lenalidomide
Affected / at Risk (%)
Total   3/11 (27.27%) 
Infections and infestations   
Lung infection † 1  2/11 (18.18%) 
Renal and urinary disorders   
Hematuria † 1  1/11 (9.09%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Siltuximab + Bortezomib + Lenalidomide
Affected / at Risk (%)
Total   11/11 (100.00%) 
Blood and lymphatic system disorders   
Anemia † 1  11/11 (100.00%) 
Neutropenia † 1  11/11 (100.00%) 
Thrombocytopenia † 1  11/11 (100.00%) 
Lymphopenia † 1  10/11 (90.91%) 
Leukopenia † 1  11/11 (100.00%) 
Leukocytosis † 1  1/11 (9.09%) 
Cardiac disorders   
Palpitations † 1  1/11 (9.09%) 
Sinus Tachycardia † 1  1/11 (9.09%) 
Ear and labyrinth disorders   
Tinnitus † 1  2/11 (18.18%) 
Endocrine disorders   
Hot Flashes † 1  1/11 (9.09%) 
Eye disorders   
Blurred Vision † 1  7/11 (63.64%) 
Dry Eye † 1  8/11 (72.73%) 
Eye Redness † 1  1/11 (9.09%) 
Eye Irritation † 1  1/11 (9.09%) 
Watering Eyes † 1  6/11 (54.55%) 
Gastrointestinal disorders   
Anorexia † 1  1/11 (9.09%) 
Constipation † 1  10/11 (90.91%) 
Dehydration † 1  1/11 (9.09%) 
Diarrhea † 1  6/11 (54.55%) 
Dysgeusia † 1  3/11 (27.27%) 
Dyspepsia † 1  1/11 (9.09%) 
Flatulence † 1  1/11 (9.09%) 
Gastritis † 1  1/11 (9.09%) 
Mucositis Oral † 1  4/11 (36.36%) 
Nausea † 1  8/11 (72.73%) 
Vomiting † 1  3/11 (27.27%) 
General disorders   
Chest Pain † 1  1/11 (9.09%) 
Edema: Limbs † 1  10/11 (90.91%) 
Edema: Trunk † 1  1/11 (9.09%) 
Fatigue † 1  11/11 (100.00%) 
Insomnia † 1  1/11 (9.09%) 
Pain (Generalized) † 1  3/11 (27.27%) 
Pain in Extremity † 1  4/11 (36.36%) 
Soreness (Bilateral) † 1  1/11 (9.09%) 
Immune system disorders   
Allergic Reaction † 1  1/11 (9.09%) 
Post Nasal Drip † 1  2/11 (18.18%) 
Infections and infestations   
Infections and Infestations: Head Boils † 1  1/11 (9.09%) 
Pneumonia † 1  1/11 (9.09%) 
Upper Respiratory Infection † 1  3/11 (27.27%) 
Investigations   
Fever † 1  1/11 (9.09%) 
Metabolism and nutrition disorders   
Alanine Aminotransferase Increased (ALT) † 1  6/11 (54.55%) 
Alanine Aminotransferase Decreased (ALT) † 1  1/11 (9.09%) 
Aspartate Aminotransferase Increased (AST) † 1  4/11 (36.36%) 
Alkaline Phosphatase Increased † 1  4/11 (36.36%) 
Alkaline Phosphatase, Decreased † 1  2/11 (18.18%) 
Blood Bilirubin Increased † 1  5/11 (45.45%) 
Blood urea nitrogen (BUN), Decreased † 1  4/11 (36.36%) 
BUN, Increased † 1  5/11 (45.45%) 
Chloride, Decreased † 1  2/11 (18.18%) 
Chloride, Increased † 1  5/11 (45.45%) 
Creatinine, Increased † 1  6/11 (54.55%) 
Creatinine, Decreased † 1  5/11 (45.45%) 
Hyperalbuminemia † 1  1/11 (9.09%) 
Hyperglycemia † 1  7/11 (63.64%) 
Hyperkalemia † 1  2/11 (18.18%) 
Hypermagnesemia † 1  1/11 (9.09%) 
Hypernatremia † 1  3/11 (27.27%) 
Hyperpophosphatemia † 1  6/11 (54.55%) 
Hyperuricemia † 1  1/11 (9.09%) 
Hypoalbuminemia † 1  7/11 (63.64%) 
Hypoglycemia † 1  5/11 (45.45%) 
Hypophosphatamia † 1  4/11 (36.36%) 
Hypouricemia † 1  5/11 (45.45%) 
Hypocalcemia † 1  8/11 (72.73%) 
Hypokalemia † 1  6/11 (54.55%) 
Hypomagnesemia † 1  7/11 (63.64%) 
Hyponatremia † 1  4/11 (36.36%) 
Lactate dehydrogenase (LDH), Decreased † 1  2/11 (18.18%) 
LDH, Increased † 1  7/11 (63.64%) 
Protein, Decreased † 1  6/11 (54.55%) 
Protein, Increased † 1  5/11 (45.45%) 
TSH, Increased † 1  2/11 (18.18%) 
Musculoskeletal and connective tissue disorders   
Bone Pain † 1  1/11 (9.09%) 
Back Pain † 1  1/11 (9.09%) 
Cramps (Calf) † 1  1/11 (9.09%) 
Facial Drooping (left) † 1  1/11 (9.09%) 
Fracture † 1  2/11 (18.18%) 
Myalgia † 1  8/11 (72.73%) 
Muscular & connective tissue Disorder- Other: Muscle Pain † 1  2/11 (18.18%) 
Nervous system disorders   
Anxiety † 1  1/11 (9.09%) 
Dizziness † 1  8/11 (72.73%) 
Headache † 1  2/11 (18.18%) 
Memory Impairment † 1  4/11 (36.36%) 
Mood Changes † 1  1/11 (9.09%) 
Paresthesia † 1  8/11 (72.73%) 
Peripheral Sensory Neuropathy † 1  3/11 (27.27%) 
Progressive Neuropathy † 1  1/11 (9.09%) 
Renal and urinary disorders   
Urinary Incontinence † 1  1/11 (9.09%) 
Reproductive system and breast disorders   
Testicular pain † 1  1/11 (9.09%) 
Respiratory, thoracic and mediastinal disorders   
Cough † 1  3/11 (27.27%) 
Dyspnea † 1  6/11 (54.55%) 
Hiccups † 1  1/11 (9.09%) 
Nasal Congestion † 1  2/11 (18.18%) 
Rhinorrhea † 1  1/11 (9.09%) 
Skin and subcutaneous tissue disorders   
Dry Skin † 1  1/11 (9.09%) 
Rash (Maculo- Papular) † 1  4/11 (36.36%) 
Vascular disorders   
Thromboembolic event † 1  1/11 (9.09%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jatin J. Shah, MD/Associate Professor, Lymphoma/Myeloma
Organization: University of Texas (UT) MD Anderson Cancer Center
Phone: 713-792-2860
EMail: CR_Study_Registration@mdanderson.org
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01531998    
Other Study ID Numbers: 2010-0073
NCI-2012-00218 ( Registry Identifier: NCI CTRP )
First Submitted: February 9, 2012
First Posted: February 13, 2012
Results First Submitted: June 2, 2015
Results First Posted: June 19, 2015
Last Update Posted: June 19, 2015