AMG 319 Lymphoid Malignancy FIH

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Amgen Identifier:
First received: January 6, 2011
Last updated: January 20, 2016
Last verified: January 2016
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 Intervention Phase
Chronic Lymphocytic Leukemia
Diffuse Large Cell Lymphoma
Hematologic Malignancies
Low Grade Lymphoma
Mantle Cell Lymphoma
Non-Hodgkin's Lymphoma
Oncology Patients
T Cell Lymphoma
Drug: AMG 319
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • PK parameters [ Time Frame: 28 Days after last subject enrolled per each cohort ] [ Designated as safety issue: Yes ]
  • Clinical/radiological response rate for CLL subjects [ Time Frame: With primary analysis ] [ Designated as safety issue: No ]
  • Treatment-emergent adverse events [ Time Frame: 28 Days after last subject enrolled per each cohort ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Phospho-AKT level in circulating CLL cells [ Time Frame: With primary analysis ] [ Designated as safety issue: No ]
  • Number of patients with clinical/radiological response [ Time Frame: With primary analysis ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: April 2011
Estimated Study Completion Date: February 2017
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01300026

United States, New Jersey
Research Site
Hackensack, New Jersey, United States, 07601
United States, North Carolina
Research Site
Durham, North Carolina, United States, 27710
United States, Utah
Research Site
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Study Director: MD Amgen
  More Information

Additional Information:
Responsible Party: Amgen Identifier: NCT01300026     History of Changes
Other Study ID Numbers: 20101262  AMG 319 FIH Lymphoid 
Study First Received: January 6, 2011
Last Updated: January 20, 2016
Health Authority: United States: Food and Drug Administration
United States: MD Anderson Surveillance Committee FWA-363
United States: Western Institutional Review Board

Keywords provided by Amgen:
Low intermediate grade B cell Lymphoma
Non-cutaneous T-cell NHL
Mantle Cell Lymphoma
PI3K delta
Chronic Lymphocytic Leukemia

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoma, B-Cell
Lymphoproliferative Disorders
Neoplasms by Histologic Type processed this record on May 26, 2016