Phase 1b Lymphoma Study of AMG 655 in Combination With Bortezomib or Vorinostat

NCT ID: NCT00791011

Last Updated: 2014-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2011-08-31

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.

Conditions

Hodgkin's Lymphoma; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Diffuse Large Cell Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 4

AMG 655 (intermediate dose) with Vorinostat

Group Type: EXPERIMENTAL

AMG 655

Intervention Type: DRUG

AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5).

Vorinostat

Intervention Type: OTHER

Vorinostat, a second generation polarplanar compound, binds to the catalytic domain of the histone deacetylases (HDAC).

Cohort 1

AMG 655 (low dose) with Bortezomib

Group Type: EXPERIMENTAL

AMG 655

Intervention Type: DRUG

AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5).

Bortezomib

Intervention Type: OTHER

A dipeptide boronic acid analogue with antineoplastic activity.

Cohort 2

AMG 655 (low dose) with vorinostat

Group Type: EXPERIMENTAL

AMG 655

Intervention Type: DRUG

AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5).

Vorinostat

Intervention Type: OTHER

Vorinostat, a second generation polarplanar compound, binds to the catalytic domain of the histone deacetylases (HDAC).

Cohort 5

AMG 655 (high dose) with Bortezomib

Group Type: EXPERIMENTAL

AMG 655

Intervention Type: DRUG

AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5).

Bortezomib

Intervention Type: OTHER

A dipeptide boronic acid analogue with antineoplastic activity.

Cohort 6

AMG 655 (high dose) with Vorinostat

Group Type: EXPERIMENTAL

AMG 655

Intervention Type: DRUG

AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5).

Vorinostat

Intervention Type: OTHER

Vorinostat, a second generation polarplanar compound, binds to the catalytic domain of the histone deacetylases (HDAC).

Cohort 7

Part 2 - Mantle Cell Lymphoma subjects only: AMG 655 at dose TBD with Bortezomib

Group Type: EXPERIMENTAL

AMG 655

Intervention Type: DRUG

AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5).

Bortezomib

Intervention Type: OTHER

A dipeptide boronic acid analogue with antineoplastic activity.

Cohort 3

AMG 655 (intermediate dose) with Bortezomib

Group Type: EXPERIMENTAL

AMG 655

Intervention Type: DRUG

AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5).

Bortezomib

Intervention Type: OTHER

A dipeptide boronic acid analogue with antineoplastic activity.

Interventions

AMG 655

AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5).

Intervention Type: DRUG

Vorinostat

Vorinostat, a second generation polarplanar compound, binds to the catalytic domain of the histone deacetylases (HDAC).

Intervention Type: OTHER

Bortezomib

A dipeptide boronic acid analogue with antineoplastic activity.

Intervention Type: OTHER

Other Intervention Names

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

References

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;

Reference Type: BACKGROUND

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;

Reference Type: BACKGROUND

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20060340

Identifier Type: -

Identifier Source: org_study_id