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
Conditions
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
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.
Interventions
DRUGAMG 319
AMG 319 is a highly selective, orally bioavailable and potent small molecule inhibitor of PI3Kδ.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Phospho-AKT level in circulating CLL cells | With primary analysis |
| Number of patients with clinical/radiological response | With primary analysis |
Countries
United States
Outcome results
None listed