AMG 319 Lymphoid Malignancy FIH

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT01300026

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

9.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: AMG 319	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2011

Actual Primary Completion Date :

Oct 1, 2013

Actual Study Completion Date :

Dec 1, 2016

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Phospho-AKT level in circulating CLL cells [With primary analysis]
Number of patients with clinical/radiological response [With primary analysis]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Hackensack	New Jersey	United States	07601
2	Research Site	Durham	North Carolina	United States	27710
3	Research Site	Salt Lake City	Utah	United States	84112