NCT01300026

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for phase_1 cancer

Timeline
Completed

Started Apr 2011

Longer than P75 for phase_1 cancer

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 6, 2011

Completed
2 months until next milestone

First Posted

Study publicly available on registry

February 21, 2011

Completed
1 month until next milestone

Study Start

First participant enrolled

April 1, 2011

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2013

Completed
3.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

February 9, 2017

Status Verified

February 1, 2017

Enrollment Period

2.5 years

First QC Date

January 6, 2011

Last Update Submit

February 8, 2017

Conditions

Keywords

Low intermediate grade B cell LymphomaNon-cutaneous T-cell NHLMantle Cell LymphomaPI3K deltaLymphoidNHLMCLHematologicCLLChronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (4)

  • 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

  • PK parameters

    28 Days after last subject enrolled per each cohort

  • Clinical/radiological response rate for CLL subjects

    With primary analysis

  • Treatment-emergent adverse events

    28 Days after last subject enrolled per each cohort

Secondary Outcomes (2)

  • Phospho-AKT level in circulating CLL cells

    With primary analysis

  • Number of patients with clinical/radiological response

    With primary analysis

Study Arms (2)

Part II Dose Expansion

EXPERIMENTAL

Dose selected from Part I dose exploration

Drug: AMG 319

Part I Dose Exploration

EXPERIMENTAL

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

Interventions

AMG 319 is a highly selective, orally bioavailable and potent small molecule inhibitor of PI3Kδ.

Part I Dose ExplorationPart II Dose Expansion

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \- 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Research Site

Hackensack, New Jersey, 07601, United States

Location

Research Site

Durham, North Carolina, 27710, United States

Location

Research Site

Salt Lake City, Utah, 84112, United States

Location

Related Links

MeSH Terms

Conditions

NeoplasmsLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Large B-Cell, DiffuseHematologic NeoplasmsLeukemiaLymphoma, Non-HodgkinLymphomaLymphoma, Mantle-CellLymphoma, T-Cell

Interventions

N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidNeoplasms by Histologic TypeHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, B-CellNeoplasms by Site

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 6, 2011

First Posted

February 21, 2011

Study Start

April 1, 2011

Primary Completion

October 1, 2013

Study Completion

December 1, 2016

Last Updated

February 9, 2017

Record last verified: 2017-02

Locations