Study of LY2127399 in Japanese Participants With Relapsed or Refactory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01556438
First received: March 15, 2012
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to evaluate the safety and effect on the body of LY2127399 in combination with bortezomib and dexamethasone in Japanese patients with relapsed or refractory multiple myeloma (MM).


Condition Intervention Phase
Multiple Myeloma
Biological: LY2127399
Drug: Bortezomib IV
Drug: Bortezomib SC
Drug: Dexamethasone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of LY2127399 in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of participants with one or more drug related adverse events (AEs) or any serious AEs [ Time Frame: Baseline up to 30 days after discontinuation of study drug (estimated to be 12 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics (PK): Maximum plasma concentration (Cmax) for LY2127399 [ Time Frame: Predose to Study Completion (estimated to be 12 months) ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK): Area under the plasma concentration-time curve from time zero to the last measurable plasma concentration (AUC0-tlast) of LY2127399 [ Time Frame: Predose to Study Completion (estimated to be 12 months) ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK): Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) of LY2127399 [ Time Frame: Predose to Study Completion (estimated to be 12 months) ] [ Designated as safety issue: No ]
  • Number of participants with tumor response (Tumor Response Rate) [ Time Frame: Baseline to Study Completion (estimated to be 12 months) ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Time from Response until Progressive Disease (estimated to be 12 months) ] [ Designated as safety issue: No ]
  • Time to progression (TTP) [ Time Frame: Baseline to date of Progressive Disease (estimated to be 12 months) ] [ Designated as safety issue: No ]
  • Pharmacodynamics (PD): Change from baseline in absolute B-cell count [ Time Frame: Baseline through study completion (estimated at 12 months) ] [ Designated as safety issue: No ]
  • Pharmacodynamics (PD): Change from baseline in B-cell subset fractions [ Time Frame: Baseline through study completion (estimated at 12 months) ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: July 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 100 mg LY2127399+BTZ IV+Dex
Cohort 1. 100 mg LY2127399 intravenously (IV) on day 1 of each cycle. 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.
Biological: LY2127399
Administered IV
Drug: Bortezomib IV
Administered IV
Drug: Dexamethasone
Administered orally
Experimental: 300 mg LY2127399+BTZ IV+Dex
Cohort 2. 300 mg LY2127399 IV on day 1 of each cycle. 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.
Biological: LY2127399
Administered IV
Drug: Bortezomib IV
Administered IV
Drug: Dexamethasone
Administered orally
Experimental: 300 mg LY2127399+BTZ SC+Dex
Cohort 2-SC. 300 mg LY2127399 IV on day 1 of each cycle. 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.
Biological: LY2127399
Administered IV
Drug: Bortezomib SC
Administered SC
Drug: Dexamethasone
Administered orally

Detailed Description:

The study has 3 cohorts. Participants will only enroll in one cohort. Cohort 2 and cohort 2-SC will be conducted in parallel.

Cohort 1 - Participants will receive 100 mg 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 LY2127399 IV, 1.3 mg/m^2 bortezomib IV, and 20 mg dexamethasone orally.

Cohort 2-SC - Participants will receive 300 mg 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

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, patient 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01556438

Locations
Japan
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.
Aichi, Japan, 467-0001
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.
Fukuoka, Japan, 811-1395
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.
Kanagawa, Japan, 259-1193
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.
Kyoto, Japan, 602-0841
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.
Tokyo, Japan, 104-0045
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01556438     History of Changes
Other Study ID Numbers: 14459, H9S-JE-JDCI
Study First Received: March 15, 2012
Last Updated: September 3, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare
Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on October 20, 2014