Phase 1b Lymphoma Study of AMG 655 in Combination With Bortezomib or Vorinostat - Full Text View

Sponsor:	Amgen
Information provided by:	Amgen
ClinicalTrials.gov Identifier:	NCT00791011

Purpose

This is a multi-center, phase 1b study of AMG 655 in combination with bortezomib or vorinostat in subjects with relapsed or refractory low grade lymphoma, mantle cell lymphoma, diffuse large cell lymphoma, and Hodgkin's disease.

Part 1 is an open-label, dose-escalation phase (3+3 design) to determine the safety, tolerability and maximum tolerated dose of AMG 655 in combination with bortezomib or vorinostat. Subjects will be enrolled into one of two arms based on investigator selection (either the bortezomib + AMG 655 arm or vorinostat + AMG 655 arm).

Part 2 of the study is a dose expansion phase that will commence after dose selection of AMG 655 in combination with bortezomib in Part 1. In Part 2, subjects (n = 20) with mantle cell lymphoma will be given AMG 655 in combination with bortezomib. The dose of AMG 655 used in combination with bortezomib will be based on safety and pharmacokinetic information obtained from Part 1 as well as from ongoing AMG 655 trials.

Condition	Intervention	Phase
Hodgkin's Lymphoma Low Grade Lymphoma Lymphoma Mantle Cell Lymphoma Non-Hodgkin's Lymphoma Diffuse Large Cell Lymphoma	Drug: AMG 655 Other: Vorinostat Other: Bortezomib	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1b Study to Evaluate the Safety and Tolerability of AMG 655 in Combination With Bortezomib or Vorinostat in Subjects With Relapsed or Refractory Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Hodgkin Disease Lymphoma

Drug Information available for: Suberoylanilide hydroxamic acid Bortezomib

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

Part 1: Safety: Subject incidence of treatment emergent adverse events, Dose Limiting Toxicities, the severity of adverse events and clinically significant changes in safety laboratory tests, physical examinations, or vital signs. [ Time Frame: Length of Study ] [ Designated as safety issue: Yes ]
Part 2: Objective response rate of AMG 655 Therapy as determined by using IWG criteria at the dose selected in Part 1, in combination with Bortezomib in subjects with mantle cell lymphoma [ Time Frame: Length of Study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Part 2: Overall survival (OS). [ Time Frame: Length of study. ] [ Designated as safety issue: No ]
Part 2: Progression-Free Survival (PFS). [ Time Frame: Length of treatment phase. ] [ Designated as safety issue: No ]
Part 2: PK parameters for AMG 655 on a 3 week dosing schedule. [ Time Frame: Treatment and follow up phase of study. ] [ Designated as safety issue: No ]
Part 2: Subject incidence of anti-AMG 655 antibody formation. [ Time Frame: Treatment and follow up phase of study. ] [ Designated as safety issue: Yes ]
Part 2: Duration of response. [ Time Frame: Length of treatment phase. ] [ Designated as safety issue: No ]
Part 1: Subject incidence of anti-AMG 655 antibody formation. [ Time Frame: Treatment and follow up phase of study. ] [ Designated as safety issue: Yes ]
Part 1: Best tumor response, objective response rate and duration of response. [ Time Frame: Length of treatment phase. ] [ Designated as safety issue: No ]
Part 1: Maximum tolerated dose of AMG 655 administered with bortezomib or vorinostat, if reached. [ Time Frame: First 21 days of treatment for each cohort. ] [ Designated as safety issue: Yes ]
Part 1: PK parameters for AMG 655 on a 3 week dosing schedule. [ Time Frame: Treatment and follow up phase of study. ] [ Designated as safety issue: No ]

Estimated Enrollment:	62
Study Start Date:	February 2008
Estimated Study Completion Date:	March 2011
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 4 AMG 655 (intermediate dose) with Vorinostat	Drug: AMG 655 AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5). Other: Vorinostat Vorinostat, a second generation polarplanar compound, binds to the catalytic domain of the histone deacetylases (HDAC). Other Name: SAHA
Experimental: Cohort 1 AMG 655 (low dose) with Bortezomib	Drug: AMG 655 AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5). Other: Bortezomib A dipeptide boronic acid analogue with antineoplastic activity. Other Name: Velcade
Experimental: Cohort 2 AMG 655 (low dose) with vorinostat	Drug: AMG 655 AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5). Other: Vorinostat Vorinostat, a second generation polarplanar compound, binds to the catalytic domain of the histone deacetylases (HDAC). Other Name: SAHA
Experimental: Cohort 5 AMG 655 (high dose) with Bortezomib	Drug: AMG 655 AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5). Other: Bortezomib A dipeptide boronic acid analogue with antineoplastic activity. Other Name: Velcade
Experimental: Cohort 6 AMG 655 (high dose) with Vorinostat	Drug: AMG 655 AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5). Other: Vorinostat Vorinostat, a second generation polarplanar compound, binds to the catalytic domain of the histone deacetylases (HDAC). Other Name: SAHA
Experimental: Cohort 7 Part 2 - Mantle Cell Lymphoma subjects only: AMG 655 at dose TBD with Bortezomib	Drug: AMG 655 AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5). Other: Bortezomib A dipeptide boronic acid analogue with antineoplastic activity. Other Name: Velcade
Experimental: Cohort 3 AMG 655 (intermediate dose) with Bortezomib	Drug: AMG 655 AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5). Other: Bortezomib A dipeptide boronic acid analogue with antineoplastic activity. Other Name: Velcade

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Part 1: Subjects must have a pathologically confirmed diagnosis of lymphoma that is relapsed or refractory to standard treatment or for which no curative therapy is available. Lymphoma subtypes that are eligible for enrollment include low grade lymphoma, mantle cell lymphoma, diffuse large cell lymphoma, and Hodgkin's disease.
Part 2: Subjects must have relapsed or refractory mantle cell lymphoma with at least one objective measurable disease site (ie, measurable in at least 2 perpendicular parameters). Subjects must have had at least one prior antineoplastic therapy, up to a maximum of 3. At least one therapy must have included an anthracycline. Subjects must have had documented relapse or progression following the last therapy (ie, most recent therapy given prior to enrollment). An abnormal PET scan will not constitute evaluable disease, unless verified by CT or MRI scan).
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate hematologic, renal, hepatic and coagulation function

Exclusion Criteria:

A history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years.
A history of allogeneic stem-cell transplantation
Primary central nervous system (CNS) tumors including primary CNS lymphoma
Central nervous system involvement by lymphoma
Myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association >class II), unstable angina, or unstable cardiac arrhythmia requiring medication
Vorinostat cohorts only: History of significant GI surgery or disease, which would impair intestinal absorption
Vorinostat cohorts only: Active peptic ulcer disease
Prior exposure to AMG 655 or other investigational TRAIL receptor agonists is not permitted
Prior treatment with bortezomib or vorinostat is not permitted for subjects enrolling in the bortezomib and vorinostat cohorts, respectively
Major surgery within 28 days before the first dose of AMG 655

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00791011

Sponsors and Collaborators

Amgen

Investigators

Study Director:

MD

Amgen

More Information

Additional Information:

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Global Development Leader, Amgen Inc.
ClinicalTrials.gov Identifier:	NCT00791011 History of Changes
Other Study ID Numbers:	20060340
Study First Received:	November 13, 2008
Last Updated:	January 20, 2011
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by Amgen:

Lymphoma
AMG 655
Trail receptor
Apoptosis

Vorinostat
Bortezomib
SAHA
Velcade

Additional relevant MeSH terms:

Hodgkin Disease
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

Lymphoma, B-Cell
Vorinostat
Bortezomib
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protease Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012