Phase 1b Lymphoma Study of AMG 655 in Combination With Bortezomib or Vorinostat
Primary Purpose
Hodgkin's Lymphoma, Low Grade Lymphoma, Lymphoma
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
AMG 655
Vorinostat
Bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Hodgkin's Lymphoma focused on measuring Lymphoma, AMG 655, Trail receptor, Apoptosis, Vorinostat, Bortezomib, SAHA, Velcade
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 4
Cohort 1
Cohort 2
Cohort 5
Cohort 6
Cohort 7
Cohort 3
Arm Description
AMG 655 (intermediate dose) with Vorinostat
AMG 655 (low dose) with Bortezomib
AMG 655 (low dose) with vorinostat
AMG 655 (high dose) with Bortezomib
AMG 655 (high dose) with Vorinostat
Part 2 - Mantle Cell Lymphoma subjects only: AMG 655 at dose TBD with Bortezomib
AMG 655 (intermediate dose) with Bortezomib
Outcomes
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.
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
Secondary Outcome Measures
Part 2: Overall survival (OS).
Part 2: Progression-Free Survival (PFS).
Part 2: PK parameters for AMG 655 on a 3 week dosing schedule.
Part 2: Subject incidence of anti-AMG 655 antibody formation.
Part 2: Duration of response.
Part 1: Subject incidence of anti-AMG 655 antibody formation.
Part 1: Best tumor response, objective response rate and duration of response.
Part 1: Maximum tolerated dose of AMG 655 administered with bortezomib or vorinostat, if reached.
Part 1: PK parameters for AMG 655 on a 3 week dosing schedule.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00791011
Brief Title
Phase 1b Lymphoma Study of AMG 655 in Combination With Bortezomib or Vorinostat
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin's Lymphoma, Low Grade Lymphoma, Lymphoma, Mantle Cell Lymphoma, Non-Hodgkin's Lymphoma, Diffuse Large Cell Lymphoma
Keywords
Lymphoma, AMG 655, Trail receptor, Apoptosis, Vorinostat, Bortezomib, SAHA, Velcade
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
AMG 655 (intermediate dose) with Vorinostat
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
AMG 655 (low dose) with Bortezomib
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
AMG 655 (low dose) with vorinostat
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
AMG 655 (high dose) with Bortezomib
Arm Title
Cohort 6
Arm Type
Experimental
Arm Description
AMG 655 (high dose) with Vorinostat
Arm Title
Cohort 7
Arm Type
Experimental
Arm Description
Part 2 - Mantle Cell Lymphoma subjects only: AMG 655 at dose TBD with Bortezomib
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
AMG 655 (intermediate dose) with Bortezomib
Intervention Type
Drug
Intervention Name(s)
AMG 655
Intervention Description
AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5).
Intervention Type
Other
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
SAHA
Intervention Description
Vorinostat, a second generation polarplanar compound, binds to the catalytic domain of the histone deacetylases (HDAC).
Intervention Type
Other
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
A dipeptide boronic acid analogue with antineoplastic activity.
Primary Outcome Measure Information:
Title
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
Title
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
Secondary Outcome Measure Information:
Title
Part 2: Overall survival (OS).
Time Frame
Length of study.
Title
Part 2: Progression-Free Survival (PFS).
Time Frame
Length of treatment phase.
Title
Part 2: PK parameters for AMG 655 on a 3 week dosing schedule.
Time Frame
Treatment and follow up phase of study.
Title
Part 2: Subject incidence of anti-AMG 655 antibody formation.
Time Frame
Treatment and follow up phase of study.
Title
Part 2: Duration of response.
Time Frame
Length of treatment phase.
Title
Part 1: Subject incidence of anti-AMG 655 antibody formation.
Time Frame
Treatment and follow up phase of study.
Title
Part 1: Best tumor response, objective response rate and duration of response.
Time Frame
Length of treatment phase.
Title
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.
Title
Part 1: PK parameters for AMG 655 on a 3 week dosing schedule.
Time Frame
Treatment and follow up phase of study.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
Citation
Younes A, Sokol L, Ribeiro de Oliveira M, Popplewell L, Romaguera JE, Copeland A, Sabin T, Hsu CP, Pan Y, Gorski K, Hwang Y, Wong S, Beaupre D, Kirschbaum MH.A Phase 1b Study Simultaneously Evaluating Two Novel Conatumumab-Based Combinations in Patients With Relapsed or Refractory Lymphoma.Journal-001239;
Results Reference
background
Citation
Younes A, Sokol L, Ribeiro de Oliveira M, Popplewell L, Romaguera JE, Copeland A, Sabin T, Hsu CP, Pan Y, Gorski K, Hwang Y, Wong S, Beaupre D, Kirschbaum MH.A Phase 1b Study Simultaneously Evaluating Two Novel Conatumumab-Based Combinations in Patients With Relapsed or Refractory Lymphoma.Journal-004521;
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Phase 1b Lymphoma Study of AMG 655 in Combination With Bortezomib or Vorinostat
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