AMG 319 Lymphoid Malignancy FIH
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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 |
- 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 ]
- 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 ]
| Estimated Enrollment: | 50 |
| Study Start Date: | February 2011 |
| Estimated Study Completion Date: | June 2014 |
| Estimated Primary Completion Date: | November 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 |
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| Contact: Amgen Call Center | 866-572-6436 |
| United States, New Jersey | |
| Research Site | Recruiting |
| Hackensack, New Jersey, United States, 07601 | |
| United States, North Carolina | |
| Research Site | Recruiting |
| Durham, North Carolina, United States, 27710 | |
| United States, Utah | |
| Research Site | Recruiting |
| Salt Lake City, Utah, United States, 84112 | |
| 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: | February 28, 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 May 19, 2013