Clinical trial NCT01300026: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2011-02-21
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Clinically significant or > or = to Grade 3 CTCAE changes in safety laboratory tests, physical exams, ECGs or vital signs
timeFrame: 28 Days after last subject enrolled per each cohort
measure: PK parameters
timeFrame: 28 Days after last subject enrolled per each cohort
measure: Clinical/radiological response rate for CLL subjects
timeFrame: With primary analysis
measure: Treatment-emergent adverse events
timeFrame: 28 Days after last subject enrolled per each cohort
Secondary outcomes:
measure: Phospho-AKT level in circulating CLL cells
timeFrame: With primary analysis
measure: Number of patients with clinical/radiological response
timeFrame: With primary analysis
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: