Clinical trial NCT01556438: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-03-16
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:
  1. positive for hepatitis B surface antigen (HBsAg+). OR
  2. positive for anti-hepatitis B core antibody and positive for hepatitis B deoxyribonucleic acid (HBV DNA).

     OR
  3. 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.

Primary outcomes:
measure: Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs
timeFrame: Baseline through 8 months
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) for Tabalumab (LY2127399)
timeFrame: Cycle 1, Day 1: 6 + or - hours after bortezomib (BTZ); Cycle 7, Day 1: immediately post BTZ dose and 2 hours after tabalumab
measure: Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Plasma Concentration (AUC0-tlast) of Tabalumab (LY2127399)
timeFrame: Cycle 1, Day 1: 6 + or - hours after bortezomib (BTZ); Cycle 7, Day 1: immediately post BTZ dose and 2 hours after tabalumab
measure: Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Tabalumab (LY2127399)
timeFrame: Cycle 1, Day 1: 6 + or - hours after bortezomib (BTZ); Cycle 7, Day 1: immediately post BTZ dose and 2 hours after tabalumab
measure: Number of Participants With Tumor Response (Tumor Response Rate)
timeFrame: Baseline to disease progression (up to 421 days)
measure: Duration of Response (DoR)
timeFrame: Time from Response until measured Progressive Disease (up to 455 days)
measure: Time to Progression (TTP)
timeFrame: Baseline to date of Progressive Disease (up to 455 days)
measure: Pharmacodynamics (PD): Change From Baseline in Absolute B-cell Count
timeFrame: Baseline through study completion (up to 455 days)
measure: Pharmacodynamics (PD): Change From Baseline in B-cell Subset Fractions
timeFrame: Baseline, Cycle 1 and Cycle 7: prior to first tabalumab dose.
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: 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
country: Japan
facility: 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
country: Japan
facility: 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
country: Japan
facility: 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
country: Japan
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
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.