Back to resultsStudy of Tabalumab (LY2127399) in Japanese Participants With Relapsed or Refactory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Tabalumab
Bortezomib IV
Bortezomib SC
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Have relapsed or refractory MM treated with at least 1 prior regimen. Prior therapy with bortezomib is allowed if there was previously at least a minimal response (MR).
Have measurable disease as defined by one or more of the following:
- serum M-protein concentration ≥ 1 g/dL (10 g/L)
- urine monoclonal light chain concentration ≥ 200 mg/24 hours as determined by urine protein electrophoresis
- involved serum free light chain (SFLC) concentration ≥ 10 mg/dL (100 mg/L) and an abnormal SFLC ratio
Have adequate organ function including:
- Absolute neutrophil count (ANC) ≥ 1000/microliter
- Platelet (PLT) count ≥ 75,000/microliter
- Hemoglobin (Hgb) ≥ 8.0 g/dL
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (if total is elevated check direct and, if normal, participant is eligible)
- Aspartate transaminase (AST) and alanine aminotransferase (ALT) are ≤ 3 x ULN
- Serum creatinine ≤ 3.0 mg/dL.
- Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of ≤ 2.
- Have discontinued all previous therapies for cancer, including chemotherapy, surgery, and radiotherapy for at least 2 weeks (6 weeks for mitomycin-C or nitrosoureas) before study enrollment and recovered from the acute effects of therapy.
- Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for 4 months following the last dose of study drug.
- Females with childbearing potential: Must have had a negative urine or serum pregnancy test <7 days before the first dose of study drug.
- Have an estimated life expectancy of ≥16 weeks, in the opinion of the investigator.
Exclusion Criteria:
- Have received treatment within 30 days of the initial dose of study drug with an experimental agent for non-cancer indications that has not received regulatory approval for any indication.
- Have one or more serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study.
- Have an uncontrolled infection.
- Females who are pregnant or breastfeeding.
Have known positive test results for human immunodeficiency virus (HIV), hepatitis B*, or hepatitis C antibodies (HCAb).
* Have evidence of or test positive for hepatitis B. A positive test for hepatitis B is 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).
- Have ≥ Grade 2 peripheral neuropathy or any grade with pain as assessed using the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v 4.03).
- Have previously received an allogenic hematopoietic stem cell transplant.
- Have previously received treatment with an experimental agent that targets B-cell activating factor (BAFF).
- Have a corrected QT (QTc) interval >470 msec on their baseline electrocardiogram (ECG).
- Have interstitial pneumonitis (interstitial pneumonia) or pulmonary fibrosis manifested as opacity on chest X-ray or computed tomography (CT) scan.
- Have had another active malignancy within the past 5 years.
Sites / Locations
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
100 mg Tabalumab+Bortezomib (BTZ)IV+Dexamethasone (Dex)
300 mg Tabalumab+BTZ IV+Dex
300 mg Tabalumab+BTZ SC+Dex
Arm Description
Cohort 1. 100 mg tabalumab (LY2127399) intravenously (IV) on day 1 of each cycle, each cyle is 21 days. Bortezomib (BTZ), 1.3 milligram per square meter (mg/m^2), IV on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dexamethasone (Dex), 20 mg/day, on day of and day after BTZ.
Cohort 2. 300 mg tabalumab (LY2127399) IV on day 1 of each cycle, each cycle is 21 days. BTZ, 1.3 mg/m^2, IV on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dex, 20 mg/day, on day of and day after BTZ.
Cohort 2-SC. 300 mg tabalumab (LY2127399)IV on day 1 of each cycle, each cycle is 21 days. BTZ, 1.3 mg/m^2, subcutaneously (SC) on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dex, 20 mg/day, on day of and day after BTZ. Cohort 2-SC was added per protocol amendment in February 2013.
Outcomes
Primary Outcome Measures
Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs
A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Secondary Outcome Measures
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) for Tabalumab (LY2127399)
Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Plasma Concentration (AUC0-tlast) of Tabalumab (LY2127399)
Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Tabalumab (LY2127399)
Number of Participants With Tumor Response (Tumor Response Rate)
Stringent Complete Response- Complete response in addition to normal free light chain ration and no clonal cells in bone marrow.
Complete Response- no monoclonal protein (mp) in blood, no serum or urine mp, less than 5% plasma cells in bone marrow.
Very Good Partial Response-more than 90% decrease in mp and urine protein. Partial Response- over 50% decrease in serum mp. Stable Disease- less than 25 percent decrease of monoclonal protein. Progressive Disease- 25% increase compared to lowest value of serum mp, urine mp, no measurable mp.
Duration of Response (DoR)
DoR is defined as the time from the date when the measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the date of first observation of measured progressive disease. For responding participants who die without progressive disease (including death from study disease),DoR will be censored at the date of death. For responding participants not known to have died as of the data cut-off date and who do not have progressive disease, DoR will be censored at the last objective progression-free assessment date prior to the data cut-off date.
Time to Progression (TTP)
TTP is defined as the time from the date of study enrollment to the date of objectively determined progressive disease. TTP will be censored at the date of the last objective progression free disease assessment.
Pharmacodynamics (PD): Change From Baseline in Absolute B-cell Count
Pharmacodynamics (PD): Change From Baseline in B-cell Subset Fractions
CD19+ peripheral B-cells counts are based on the percentage of total leukocyte population and absolute cell counts.
Full Information
NCT ID
NCT01556438
First Posted
March 15, 2012
Last Updated
November 20, 2018
Sponsor
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT01556438
Brief Title
Study of Tabalumab (LY2127399) in Japanese Participants With Relapsed or Refactory Multiple Myeloma
Official Title
A Phase 1 Study of Tabalumab (LY2127399) in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
August 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and effect on the body of Tabalumab (LY2127399) in combination with bortezomib and dexamethasone in Japanese participants with relapsed or refractory multiple myeloma (MM).
Detailed Description
The study has 3 cohorts. Cohort 2 and cohort 2-SC will be conducted in parallel with some data presented combined.
Cohort 1 - Participants will receive 100 mg Tabalumab (LY2127399) intravenously (IV), 1.3 milligram per square meter (mg/m^2) bortezomib IV, and 20 mg dexamethasone orally.
Cohort 2 - Participants will receive 300 mg Tabalumab (LY2127399) IV, 1.3 mg/m^2 bortezomib IV, and 20 mg dexamethasone orally.
Cohort 2-SC - Participants will receive 300 mg Tabalumab (LY2127399) IV, 1.3 mg/m^2 bortezomib subcutaneously (SC), and 20 mg dexamethasone orally.
Cohort 2-SC was added per protocol amendment in February 2013.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
100 mg Tabalumab+Bortezomib (BTZ)IV+Dexamethasone (Dex)
Arm Type
Experimental
Arm Description
Cohort 1. 100 mg tabalumab (LY2127399) intravenously (IV) on day 1 of each cycle, each cyle is 21 days. Bortezomib (BTZ), 1.3 milligram per square meter (mg/m^2), IV on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dexamethasone (Dex), 20 mg/day, on day of and day after BTZ.
Arm Title
300 mg Tabalumab+BTZ IV+Dex
Arm Type
Experimental
Arm Description
Cohort 2. 300 mg tabalumab (LY2127399) IV on day 1 of each cycle, each cycle is 21 days. BTZ, 1.3 mg/m^2, IV on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dex, 20 mg/day, on day of and day after BTZ.
Arm Title
300 mg Tabalumab+BTZ SC+Dex
Arm Type
Experimental
Arm Description
Cohort 2-SC. 300 mg tabalumab (LY2127399)IV on day 1 of each cycle, each cycle is 21 days. BTZ, 1.3 mg/m^2, subcutaneously (SC) on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dex, 20 mg/day, on day of and day after BTZ. Cohort 2-SC was added per protocol amendment in February 2013.
Intervention Type
Biological
Intervention Name(s)
Tabalumab
Other Intervention Name(s)
LY2127399
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Bortezomib IV
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Bortezomib SC
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Administered orally
Primary Outcome Measure Information:
Title
Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs
Description
A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time Frame
Baseline through 8 months
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) for Tabalumab (LY2127399)
Time Frame
Cycle 1, Day 1: 6 + or - hours after bortezomib (BTZ); Cycle 7, Day 1: immediately post BTZ dose and 2 hours after tabalumab
Title
Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Plasma Concentration (AUC0-tlast) of Tabalumab (LY2127399)
Time Frame
Cycle 1, Day 1: 6 + or - hours after bortezomib (BTZ); Cycle 7, Day 1: immediately post BTZ dose and 2 hours after tabalumab
Title
Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Tabalumab (LY2127399)
Time Frame
Cycle 1, Day 1: 6 + or - hours after bortezomib (BTZ); Cycle 7, Day 1: immediately post BTZ dose and 2 hours after tabalumab
Title
Number of Participants With Tumor Response (Tumor Response Rate)
Description
Stringent Complete Response- Complete response in addition to normal free light chain ration and no clonal cells in bone marrow.
Complete Response- no monoclonal protein (mp) in blood, no serum or urine mp, less than 5% plasma cells in bone marrow.
Very Good Partial Response-more than 90% decrease in mp and urine protein. Partial Response- over 50% decrease in serum mp. Stable Disease- less than 25 percent decrease of monoclonal protein. Progressive Disease- 25% increase compared to lowest value of serum mp, urine mp, no measurable mp.
Time Frame
Baseline to disease progression (up to 421 days)
Title
Duration of Response (DoR)
Description
DoR is defined as the time from the date when the measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the date of first observation of measured progressive disease. For responding participants who die without progressive disease (including death from study disease),DoR will be censored at the date of death. For responding participants not known to have died as of the data cut-off date and who do not have progressive disease, DoR will be censored at the last objective progression-free assessment date prior to the data cut-off date.
Time Frame
Time from Response until measured Progressive Disease (up to 455 days)
Title
Time to Progression (TTP)
Description
TTP is defined as the time from the date of study enrollment to the date of objectively determined progressive disease. TTP will be censored at the date of the last objective progression free disease assessment.
Time Frame
Baseline to date of Progressive Disease (up to 455 days)
Title
Pharmacodynamics (PD): Change From Baseline in Absolute B-cell Count
Time Frame
Baseline through study completion (up to 455 days)
Title
Pharmacodynamics (PD): Change From Baseline in B-cell Subset Fractions
Description
CD19+ peripheral B-cells counts are based on the percentage of total leukocyte population and absolute cell counts.
Time Frame
Baseline, Cycle 1 and Cycle 7: prior to first tabalumab dose.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have relapsed or refractory MM treated with at least 1 prior regimen. Prior therapy with bortezomib is allowed if there was previously at least a minimal response (MR).
Have measurable disease as defined by one or more of the following:
serum M-protein concentration ≥ 1 g/dL (10 g/L)
urine monoclonal light chain concentration ≥ 200 mg/24 hours as determined by urine protein electrophoresis
involved serum free light chain (SFLC) concentration ≥ 10 mg/dL (100 mg/L) and an abnormal SFLC ratio
Have adequate organ function including:
Absolute neutrophil count (ANC) ≥ 1000/microliter
Platelet (PLT) count ≥ 75,000/microliter
Hemoglobin (Hgb) ≥ 8.0 g/dL
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (if total is elevated check direct and, if normal, participant is eligible)
Aspartate transaminase (AST) and alanine aminotransferase (ALT) are ≤ 3 x ULN
Serum creatinine ≤ 3.0 mg/dL.
Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of ≤ 2.
Have discontinued all previous therapies for cancer, including chemotherapy, surgery, and radiotherapy for at least 2 weeks (6 weeks for mitomycin-C or nitrosoureas) before study enrollment and recovered from the acute effects of therapy.
Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for 4 months following the last dose of study drug.
Females with childbearing potential: Must have had a negative urine or serum pregnancy test <7 days before the first dose of study drug.
Have an estimated life expectancy of ≥16 weeks, in the opinion of the investigator.
Exclusion Criteria:
Have received treatment within 30 days of the initial dose of study drug with an experimental agent for non-cancer indications that has not received regulatory approval for any indication.
Have one or more serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study.
Have an uncontrolled infection.
Females who are pregnant or breastfeeding.
Have known positive test results for human immunodeficiency virus (HIV), hepatitis B*, or hepatitis C antibodies (HCAb).
* Have evidence of or test positive for hepatitis B. A positive test for hepatitis B is 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).
Have ≥ Grade 2 peripheral neuropathy or any grade with pain as assessed using the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v 4.03).
Have previously received an allogenic hematopoietic stem cell transplant.
Have previously received treatment with an experimental agent that targets B-cell activating factor (BAFF).
Have a corrected QT (QTc) interval >470 msec on their baseline electrocardiogram (ECG).
Have interstitial pneumonitis (interstitial pneumonia) or pulmonary fibrosis manifested as opacity on chest X-ray or computed tomography (CT) scan.
Have had another active malignancy within the past 5 years.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Aichi
ZIP/Postal Code
467-0001
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Kanagawa
ZIP/Postal Code
259-1193
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Kyoto
ZIP/Postal Code
602-0841
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
27350068
Citation
Iida S, Ogiya D, Abe Y, Taniwaki M, Asou H, Maeda K, Uenaka K, Nagaoka S, Ishiki T, Conti I, Tobinai K. Dose-escalation study of tabalumab with bortezomib and dexamethasone in Japanese patients with multiple myeloma. Cancer Sci. 2016 Sep;107(9):1281-9. doi: 10.1111/cas.13000. Epub 2016 Sep 1.
Results Reference
derived
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Study of Tabalumab (LY2127399) in Japanese Participants With Relapsed or Refactory Multiple Myeloma
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