AMG 319 Lymphoid Malignancy FIH

Amgen

Status and phase: Completed; Phase 1

Conditions: Oncology; T Cell Lymphoma; Mantle Cell Lymphoma; Cancer; Leukemia; Oncology Patients; Tumors; Hematology; Non-Hodgkin's Lymphoma; Low Grade Lymphoma; Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; Hematologic Malignancies

Treatments: Drug: AMG 319

Study type: Interventional

Funder types: Industry

Identifiers

NCT01300026

AMG 319 FIH Lymphoid

20101262

Details and patient eligibility

About

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.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

Part II Dose Expansion

Experimental group

Description:

Dose selected from Part I dose exploration

Treatment:

Drug: AMG 319

Part I Dose Exploration

Experimental group

Description:

The AMG 319 doses proposed for this study are 25, 50, 100, 200, 300 and 400 mg administered by mouth once daily.

Treatment:

Drug: AMG 319