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AMG 319 Lymphoid Malignancy FIH

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01300026
Recruitment Status : Completed
First Posted : February 21, 2011
Last Update Posted : February 10, 2017
Information provided by (Responsible Party):

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

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Study Type : Interventional  (Clinical Trial)
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 : April 2011
Actual Primary Completion Date : October 2013
Actual Study Completion Date : December 2016

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.

Primary Outcome Measures :
  1. 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 ]
  2. PK parameters [ Time Frame: 28 Days after last subject enrolled per each cohort ]
  3. Clinical/radiological response rate for CLL subjects [ Time Frame: With primary analysis ]
  4. Treatment-emergent adverse events [ Time Frame: 28 Days after last subject enrolled per each cohort ]

Secondary Outcome Measures :
  1. Phospho-AKT level in circulating CLL cells [ Time Frame: With primary analysis ]
  2. Number of patients with clinical/radiological response [ Time Frame: With primary analysis ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01300026

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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
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen Identifier: NCT01300026    
Other Study ID Numbers: 20101262
AMG 319 FIH Lymphoid
First Posted: February 21, 2011    Key Record Dates
Last Update Posted: February 10, 2017
Last Verified: February 2017
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:
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Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Hematologic Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, B-Cell
Neoplasms by Site
Hematologic Diseases
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action