A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Tabalumab in Combination With Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 220
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS)
Study Overview
Brief Summary
The purpose of this study is to evaluate an investigational drug called tabalumab in participants with Multiple Myeloma (MM) who have tried at least one other therapy in the past. Tabalumab will be given in combination with standard doses of two other drugs that are often used to treat MM. Study doctors will collect information about the effectiveness and side effects of this therapy.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have symptomatic and/or progressive MM that was previously treated with at least 1 and no more than 3 prior lines of therapy
- •Have measurable disease
- •Have given written informed consent prior to any study-specific procedures
- •Have adequate organ function
- •Treatment with prior autologous transplant is permitted
Exclusion Criteria
- •Are enrolled in or discontinued from a clinical trial of any drug or device within 21 days prior to the first dose of assigned study treatment
- •Have had less than a minimal response or have had progressive disease within 60 days of most recent therapy with a proteasome inhibitor
- •Plan to proceed to autologous transplant for consolidation after participation in this trial
- •Have an active infection or ongoing treatment for systemic infection ("ongoing treatment" does not include prophylactic anti-infectives),, chest x-ray suggestive of tuberculosis, or history/risk of chronic/latent infection that may reactivate in the presence of study therapy
- •Have any of the following:
- •positive test results for human immunodeficiency virus (HIV)
- •positive test for hepatitis B, defined as positive for hepatitis B surface antigen (HBsAg+), OR positive for anti-hepatitis B core antibody AND positive for hepatitis B deoxyribonucleic acid (HBV DNA), OR positive for anti-hepatitis B surface antibody (HBsAb+) AND positive for hepatitis B deoxyribonucleic acid (HBV DNA)
- •positive test results for hepatitis C virus (HCV), defined as positive for hepatitis C antibody (HepCAb) AND confirmed positive via the hepatitis C recombinant immunoblot assay
- •Have had significant allergy to human/humanized monoclonal antibodies that, in the opinion of the investigator, poses an unacceptable risk to the participants
- •Have known hypersensitivity or contraindication to any of the study therapies or excipients
- •Prior allogeneic hematopoietic stem cell transplant
- •Prior therapy with experimental agents targeting B-cell activating factor (BAFF), including LY2127399
- •Have corrected QT (QTc) interval >500 millisecond (msec) on baseline 12-lead electrocardiogram (ECG)
- •Have Waldenstrom's macroglobulinemia
- •History of malignancy with adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer, are eligible regardless of the time of diagnosis/treatment
Arms & Interventions
100 mg Tabalumab+Dexamethasone (Dex)+Bortezomib (BTZ)
Tabalumab 100 milligram (mg) administered once intravenously (IV) over 30 minutes on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.
Bortezomib 1.3 milligram per square meter (mg/m^2) administered once subcutaneously (SQ) on Days 1, 4, 8 and 11 every 21 days for a minimum 8 cycles.
All treatment may continue past 8 cycles.
Intervention: Dexamethasone (Drug)
100 mg Tabalumab+Dexamethasone (Dex)+Bortezomib (BTZ)
Tabalumab 100 milligram (mg) administered once intravenously (IV) over 30 minutes on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.
Bortezomib 1.3 milligram per square meter (mg/m^2) administered once subcutaneously (SQ) on Days 1, 4, 8 and 11 every 21 days for a minimum 8 cycles.
All treatment may continue past 8 cycles.
Intervention: Bortezomib (Drug)
100 mg Tabalumab+Dexamethasone (Dex)+Bortezomib (BTZ)
Tabalumab 100 milligram (mg) administered once intravenously (IV) over 30 minutes on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.
Bortezomib 1.3 milligram per square meter (mg/m^2) administered once subcutaneously (SQ) on Days 1, 4, 8 and 11 every 21 days for a minimum 8 cycles.
All treatment may continue past 8 cycles.
Intervention: Tabalumab (Biological)
300 mg Tabalumab+Dexamethasone+Bortezomib
Tabalumab 300 mg administered once IV over 30 minutes on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for a minimum 8 cycles.
Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.
All treatment may continue past 8 cycles.
Intervention: Dexamethasone (Drug)
300 mg Tabalumab+Dexamethasone+Bortezomib
Tabalumab 300 mg administered once IV over 30 minutes on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for a minimum 8 cycles.
Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.
All treatment may continue past 8 cycles.
Intervention: Bortezomib (Drug)
300 mg Tabalumab+Dexamethasone+Bortezomib
Tabalumab 300 mg administered once IV over 30 minutes on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for a minimum 8 cycles.
Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.
All treatment may continue past 8 cycles.
Intervention: Tabalumab (Biological)
Placebo Comparator: Placebo + Dexamethasone + Bortezomib
Placebo administered once IV on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for a minimum 8 cycles.
Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.
All treatment may continue past 8 cycles.
Intervention: Placebo (Drug)
Placebo Comparator: Placebo + Dexamethasone + Bortezomib
Placebo administered once IV on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for a minimum 8 cycles.
Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.
All treatment may continue past 8 cycles.
Intervention: Dexamethasone (Drug)
Placebo Comparator: Placebo + Dexamethasone + Bortezomib
Placebo administered once IV on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for a minimum 8 cycles.
Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.
All treatment may continue past 8 cycles.
Intervention: Bortezomib (Drug)
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: Baseline up to Objective Disease Progression or Death From Any Cause (assessed up to 9 months)
PFS is defined as the time from date of first dose to the first observation of disease progression or death due to any cause. If a participant does not have a complete baseline disease assessment, then the PFS time is censored at the enrollment date, regardless of whether or not objectively determined disease progression (Increase of \> 25% from lowest response in serum M component, urine M component, bone marrow plasma cell percentage, development of bone lesions) or death has been observed for the participant. If a participant is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time is censored at the last complete objective progression-free disease assessment date.
Secondary Outcomes
- Overall Survival(Baseline to Death From Any Cause (assessed up to 19 months))
- Number of Participants With >30% Reduction in Brief Pain Inventory (BPI) - Worst Pain Score(Baseline through End of Treatment (19 months))
- Time to Progression (TTP)(Baseline to Objective Disease Progression or Death (assessed up to 9 months))
- Time to First Skeletal-Related Event (SRE)(Baseline to Date of First Skeletal Related Event (assessed up to 19 months))
- Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab(Cycle (C)1 Day (D)1: Predose, 3O minutes, 2 hours Postdose; C1 D4, 8, 11: Predose, (D11 only, 30 minutes Postdose); C2 and C6-C10 D1: Predose and immediately Postdose; C2 D 4, 8, 11: Anytime)
- PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab(C1 D1: Predose, 3O minutes, 2 hours Postdose; C1 D4, 8, 11: Predose, (D11 only, 30 minutes Postdose); C2 and C6-C10 D1: Predose and immediately Postdose; C2 D 4, 8, 11: Anytime)
- PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab(C1 D1: Predose, 3O minutes, 2 hours Postdose; C1 D4, 8, 11: Predose, (D11 only, 30 minutes Postdose); C2 and C6-C10 D1: Predose and immediately Postdose; C2 D 4, 8, 11: Anytime)
- Duration of Response (DoR)(Time from Response to Objective Disease Progression (assessed up to 38 months))
- Time to Next Treatment (TNT)(Baseline to Initiation of New Cancer Treatment or Death From Any Cause (18 Months))
- Number of Participants Developing Anti-tabalumab Antibodies(Baseline through Cycle 8)
- Participants With Best Overall Response (BOR) in Each Category(Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (28 Months))
- Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR])(Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (up to 28 Months))
- Overall Response Rate (ORR)(Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (28 Months))