AMG 319 Lymphoid Malignancy FIH

February 8, 2017 updated by: Amgen

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Research Site
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

- 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part II Dose Expansion
Dose selected from Part I dose exploration
Drug: AMG 319
AMG 319 is a highly selective, orally bioavailable and potent small molecule inhibitor of PI3Kδ.
Experimental: Part I Dose Exploration
The AMG 319 doses proposed for this study are 25, 50, 100, 200, 300 and 400 mg administered by mouth once daily.
Drug: AMG 319
AMG 319 is a highly selective, orally bioavailable and potent small molecule inhibitor of PI3Kδ.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
Phospho-AKT level in circulating CLL cells
Time Frame: With primary analysis
With primary analysis
Number of patients with clinical/radiological response
Time Frame: With primary analysis
With primary analysis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2011

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

January 6, 2011

First Submitted That Met QC Criteria

February 17, 2011

First Posted (Estimate)

February 21, 2011

Study Record Updates

Last Update Posted (Estimate)

February 9, 2017

Last Update Submitted That Met QC Criteria

February 8, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20101262
  • AMG 319 FIH Lymphoid

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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