AMG 319 Lymphoid Malignancy FIH

Cancer Clinical Trial

Official title:

A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 319 in Adult Subjects With Relapsed or Refractory Lymphoid Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01300026
• Other study ID #: 20101262
• Secondary ID: AMG 319 FIH Lymp
• Status: Completed
• Phase: Phase 1
• First received: January 6, 2011
• Last updated: February 8, 2017
• Start date: April 2011
• Est. completion date: December 2016

Study information

• Verified date: February 2017
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2016
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• Chronic Lymphocytic Leukemia
• Diffuse Large Cell Lymphoma
• Hematologic Malignancies
• Hematology
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Low Grade Lymphoma
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Mantle Cell Lymphoma
• Neoplasms
• Non-Hodgkin's Lymphoma
• Oncology
• Oncology Patients
• T Cell Lymphoma
• Tumors

Intervention

Drug:
• AMG 319
AMG 319 is a highly selective, orally bioavailable and potent small molecule inhibitor of PI3Kd.

Locations

Country	Name	City	State
United States	Research Site	Durham	North Carolina
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	PK parameters		28 Days after last subject enrolled per each cohort
Primary	Clinical/radiological response rate for CLL subjects		With primary analysis
Primary	Treatment-emergent adverse events		28 Days after last subject enrolled per each cohort
Secondary	Phospho-AKT level in circulating CLL cells		With primary analysis
Secondary	Number of patients with clinical/radiological response		With primary analysis

External Links

•   AmgenTrials clinical trials website