AMG 319 Lymphoid Malignancy FIH

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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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

Intervention / Treatment
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* Drug: AMG 319


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part II Dose Expansion<br>Dose selected from Part I dose exploration | Drug: AMG 319<br>* AMG 319 is a highly selective, orally bioavailable and potent small molecule inhibitor of PI3Kδ.<br>|
| Experimental: Part I Dose Exploration<br>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<br>* AMG 319 is a highly selective, orally bioavailable and potent small molecule inhibitor of PI3Kδ.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phospho-AKT level in circulating CLL cells |  | With primary analysis | 
| Number of patients with clinical/radiological response |  | With primary analysis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low intermediate grade B cell Lymphoma, Non-cutaneous T-cell NHL, Mantle Cell Lymphoma, PI3K delta, Lymphoid, NHL, MCL, Hematologic, CLL, Chronic Lymphocytic Leukemia