AMG 319 Lymphoid Malignancy FIH

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01300026
First received: January 6, 2011
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

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
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 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: June 2014
Primary Completion Date: May 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01300026

Locations
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
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01300026     History of Changes
Other Study ID Numbers: 20101262, AMG 319 FIH Lymphoid
Study First Received: January 6, 2011
Last Updated: November 19, 2013
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
Lymphoid
NHL
MCL
Hematologic
CLL
Chronic Lymphocytic Leukemia

Additional relevant MeSH terms:
Neoplasms
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Lymphoma, T-Cell
Lymphoma, Mantle-Cell
Hematologic Neoplasms
Neoplasms by Histologic Type
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Neoplasms by Site
Hematologic Diseases

ClinicalTrials.gov processed this record on April 16, 2014