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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00791011
• Other study ID #: 20060340
• Status: Completed
• Phase: Phase 1
• First received: November 13, 2008
• Last updated: March 3, 2014
• Start date: February 2008
• Est. completion date: August 2011

Study information

• Verified date: March 2014
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: August 2011
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diffuse Large Cell Lymphoma
• Hodgkin Disease
• Hodgkin's Lymphoma
• Low Grade Lymphoma
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Mantle Cell Lymphoma
• Non-Hodgkin's Lymphoma

Intervention

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).
• Bortezomib
A dipeptide boronic acid analogue with antineoplastic activity.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (2)

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;

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;

Outcome

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

External Links

•   AmgenTrials clinical trials website