AMG 319 Lymphoid Malignancy FIH

Phase 1

Completed

• Conditions: Cancer; Chronic Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; Hematologic Malignancies; Hematology; Leukemia; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma
• Interventions: Drug: AMG 319

• Registration Number: NCT01300026
• Lead Sponsor: Amgen

Brief Summary

This is a multi-center, phase 1, open-label first-in-human study of AMG 319 in subjects with relapsed or refractory lymphoid malignancies. This study consists of two parts. The dose exploration in part 1, studies cohorts of 3 subjects with relapsed or refractory lymphoid malignancies and uses a practical continuous reassessment model \[CRM\] to guide dose escalation and to define the MTD. The dose expansion in part 2 will enroll 20 subjects with CLL at a dose no higher than the MTD and further explore the safety, PK, and clinical activity of AMG 319 in this patient population.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-01-06
• Study First Submitted QC: 2011-02-17
• Study First Posted: 2011-02-21
• Study Start: 2011-04
• Primary Completion: 2013-10
• Study Completion: 2016-12
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-08
• Last Update Posted: 2017-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

• Part 1 (Dose Exploration): Relapsed or refractory lymphoid malignancy of the following type for which standard treatment does not exist or is no longer effective:

B-cell Chronic Lymphocytic Leukemia (CLL) confirmed by immunophenotype or Non-Hodgkin Lymphoma: Low or intermediate grade B-cell NHL, mantle cell lymphoma, non-cutaneous T-cell NHL confirmed by histology and/or immunophenotype

• Part 2 (Dose Expansion): Subjects must have relapsed or refractory B-cell Chronic Lymphocytic Leukemia confirmed by immunophenotype for which standard treatment does not exist or is no longer effective.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Life expectancy of > 3 months, in the opinion of the investigator
• Men or women ≥ 18 years old
• Hematological function, as follows:

Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (unless due to disease-related bone marrow involvement as documented by bone marrow biopsy, ≥ 0.5 x 109/L) Platelet count ≥ 50 x 109/L (without a transfusion within 14 days before enrollment) Hemoglobin ≥ 9 g/dL

• Hepatic function, as follows: Aspartate aminotransferase (AST) < 3.0 x ULN Alanine aminotransferase (ALT) < 3.0 x ULN Alkaline phosphatase (ALP) < 2.0 x ULN (< 5 x ULN in subjects whom the PI and sponsor agree that clinical data suggest an extrahepatic source of elevation) Total bilirubin < 1.5 x ULN (< 3.0 x ULN for subjects with documented Gilbert's Disease or for whom the indirect bilirubin level suggests an extrahepatic source of elevation) Amylase ≤ 2.0 x IULN Lipase ≤ 2.0 x IULN

Exclusion Criteria

• Primary or disseminated tumor involving the central nervous system (CNS)
• A history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years
• History of allogeneic stem-cell (or other organ) transplantation
• Clinically significant ECG changes which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome
• QTcF interval > 470 msec
• Active or chronic hepatitis B or hepatitis C infection, determined by serologic tests
• Recent infection requiring intravenous anti-infective treatment that was completed ≤ 14 days before enrollment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part II Dose Expansion	AMG 319	Dose selected from Part I dose exploration
Part I Dose Exploration	AMG 319	The AMG 319 doses proposed for this study are 25, 50, 100, 200, 300 and 400 mg administered by mouth once daily.

Primary Outcome Measures

Name	Time	Method
Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vital signs	28 Days after last subject enrolled per each cohort
Treatment-emergent adverse events	28 Days after last subject enrolled per each cohort
PK parameters	28 Days after last subject enrolled per each cohort
Clinical/radiological response rate for CLL subjects	With primary analysis

Secondary Outcome Measures

Name	Time	Method
Number of patients with clinical/radiological response	With primary analysis
Phospho-AKT level in circulating CLL cells	With primary analysis

Trial Locations

Locations (1)

Research Site; 🇺🇸 Salt Lake City, Utah, United States