A Phase 1 Safety Study of LY2127399 in Combination With Bortezomib

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00689507
• Other study ID #: H9S-MC-JDCF
• Status: Completed
• Phase: Phase 1
• First received: May 29, 2008
• Last updated: June 25, 2015
• Start date: March 2008
• Est. completion date: May 2014

Study information

• Verified date: May 2015
• Source: Applied Molecular Evolution
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: May 2014
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• LY2127399
monoclonal antibody

Locations

Country	Name	City	State
United States	University of Alabama	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	UCLA	Los Angeles	California
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Applied Molecular Evolution	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK)/Pharmacodynamic (PD)modeling of LY2127399 to determine a Phase 2 dose		2 years	Yes
Secondary	Safety and toxicity profile for LY2127399 in combination with bortezomib		2 years	Yes
Secondary	Response rate, duration of response, and time to progression of LY2127399 in combination with bortezomib		2 years	No
Secondary	Response rate, duration of response, and time to progression of LY2127399 as a single-agent		2 years	No