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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

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

NCT ID

NCT00791011

First Posted

November 13, 2008

Last Updated

March 3, 2014

Sponsor

Amgen

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

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

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

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

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Citation

Results Reference

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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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