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AMG 319 Lymphoid Malignancy FIH

Primary Purpose

Cancer, Chronic Lymphocytic Leukemia, Diffuse Large Cell Lymphoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

AMG 319

About this trial

This is an interventional treatment trial for Cancer focused on measuring Low intermediate grade B cell Lymphoma, Non-cutaneous T-cell NHL, Mantle Cell Lymphoma, PI3K delta, Lymphoid, NHL, MCL, Hematologic, CLL, Chronic Lymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Research Site
Research Site
Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part II Dose Expansion

Part I Dose Exploration

Arm Description

Dose selected from 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.

Outcomes

Primary Outcome Measures

Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vital signs

PK parameters

Clinical/radiological response rate for CLL subjects

Treatment-emergent adverse events

Secondary Outcome Measures

Phospho-AKT level in circulating CLL cells

Number of patients with clinical/radiological response

Full Information

NCT ID

NCT01300026

First Posted

January 6, 2011

Last Updated

February 8, 2017

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT01300026

Brief Title

AMG 319 Lymphoid Malignancy FIH

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Completed

Study Start Date

April 2011 (undefined)

Primary Completion Date

October 2013 (Actual)

Study Completion Date

December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Low intermediate grade B cell Lymphoma, Non-cutaneous T-cell NHL, Mantle Cell Lymphoma, PI3K delta, Lymphoid, NHL, MCL, Hematologic, CLL, Chronic Lymphocytic Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part II Dose Expansion

Arm Type

Experimental

Arm Description

Dose selected from Part I dose exploration

Arm Title

Part I Dose Exploration

Arm Type

Experimental

Arm Description

The AMG 319 doses proposed for this study are 25, 50, 100, 200, 300 and 400 mg administered by mouth once daily.

Intervention Type

Drug

Intervention Name(s)

AMG 319

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Title

PK parameters

Time Frame

28 Days after last subject enrolled per each cohort

Title

Clinical/radiological response rate for CLL subjects

Time Frame

With primary analysis

Title

Treatment-emergent adverse events

Time Frame

28 Days after last subject enrolled per each cohort

Secondary Outcome Measure Information:

Title

Phospho-AKT level in circulating CLL cells

Time Frame

With primary analysis

Title

Number of patients with clinical/radiological response

Time Frame

With primary analysis

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

Research Site

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Research Site

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84112

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

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AMG 319 Lymphoid Malignancy FIH

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