A Phase 1 Safety Study of LY2127399 in Combination With Bortezomib

A Phase 1 Safety Study of LY2127399 in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma

H9S-MC-JDCF was a multicenter non-randomized, single-arm, open-label, dose-escalation, dose confirmation, Phase 1 study of intravenous (IV) LY2127399 in combination with bortezomib in patients with refractory or relapsed MM.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: LY2127399

Detailed Description

This is a study of a drug known as LY2127399, which will be given with a common treatment for multiple myeloma called bortezomib (Velcade). The primary purpose of this study is to (1)Determine the safety of LY2127399 in combination with bortezomib and any side effects that might be associated with it; (2)Assess whether LY2127399 in combination with bortezomib may help patients with relapsed or refractory multiple myeloma; (3)How much LY2127399 should be given to patients along with bortezomib.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University Of Alabama
  • California
    • Los Angeles, California, United States, 90024
      • UCLA
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have relapsed or refractory multiple myeloma treated with at least 1 prior regimen. Prior therapy with bortezomib is allowed if there has been no relapse or progression within 3 months of the last dose of bortezomib, and bortezomib is considered by the treating physician to be a reasonable therapy for the patient.

• Have measurable disease defined by one or more of the following:

  • Monoclonal protein in the serum of ≥1 g/dL (10 g/L).
  • Monoclonal light chain in the urine protein electrophoresis of ≥ 200 mg/24 hours.
  • Involved Serum Free Light Chain (SFLC) level > 10 mg/dL (100 mg/L) provided SFLC ratio is abnormal.
  • Measurable plasmacytoma.
• Are ≥ 18 years of age.
• Have given written informed consent prior to any study-specific procedures

• Have adequate organ function including:

  • Absolute neutrophil count (ANC) ≥ 1000/microliter
  • Platelet (PLT) count ≥ 50,000/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) ≤ 3 x ULN
  • Creatinine ≤ 3.0 mg/dl.
• Have a performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale (refer to Attachment JDCF.5).
• Have discontinued all previous therapies for cancer, including chemotherapy and radiotherapy at least 2 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy.
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
• Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 4 months following the last dose of study drug.
• Females with child bearing potential must have had a negative urine or serum pregnancy test ≤ 3 days prior to the first dose of study drug.
• Have an estimated life expectancy of ≥ 16 weeks.
• Treatment with prior autologous transplant is permitted. If a transplant is used as consolidation following chemotherapy, without intervening disease progression, it will be considered one line of treatment with the preceding chemotherapy.

Exclusion Criteria:

• Have received treatment within 30 days of the initial dose of study drug with a drug 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 uncontrolled infection.
• Females who are pregnant or lactating.
• Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb).
• Have peripheral neuropathy of > Grade 2, or of any grade with pain, as measured by CTCAE v3.0.
• Previously treated with LY2127399, or have had significant allergy to humanized monoclonal antibodies that, in the opinion of the investigator, poses an increased risk to the patient.
• Prior allogeneic hematopoietic stem cell transplant.
• Prior therapy with experimental agents targeting BAFF.
• Have QTc interval > 450 msec on baseline 12-lead ECG.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Phase(Part A): 1,10, 30, 100 or 300 mg of LY2127399 IV on day 1 of specific 21 day cycles and 1.3 mg/m2 Bortezomib IV on days 1, 4, 8, and 11 of each 21 day cycle	Biological: LY2127399; monoclonal antibody
Experimental: Dose Confirmation Phase (Part B1): Dose determined by PK/PD modeling, LY2127399 IV on day 2 of Cycle 1 and on day 1 of specific cycles and 1.3 mg/m2 Bortezomib IV on days 1, 4, 8, and 11 of each cycle	Biological: LY2127399; monoclonal antibody
Experimental: Dose Confirmation Phase (Part B2): Dose determined by PK/PD modeling, LY2127399 IV on day 1 of specific cycles and 1.3 mg/m2 Bortezomib IV on days 1, 4, 8, and 11 of specific cycles	Biological: LY2127399; monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic (PK)/Pharmacodynamic (PD)modeling of LY2127399 to determine a Phase 2 dose	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and toxicity profile for LY2127399 in combination with bortezomib	2 years
Response rate, duration of response, and time to progression of LY2127399 in combination with bortezomib	2 years
Response rate, duration of response, and time to progression of LY2127399 as a single-agent	2 years

Collaborators and Investigators

• Sponsor: Applied Molecular Evolution
• Collaborators: Eli Lilly and Company
• Investigators: Study Director: Susan Carpenter, PhD, Applied Molecular Evolution

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: May 29, 2008
• First Submitted That Met QC Criteria: May 29, 2008
• First Posted (Estimate): June 3, 2008

Study Record Updates

• Last Update Posted (Estimate): June 29, 2015
• Last Update Submitted That Met QC Criteria: June 25, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Relapsed; Refractory; Bortezomib; Velcade
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: H9S-MC-JDCF