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

NCT00791011 | Completed Phase 1

• 1 other identifier: 20060340
• Study Type: interventional
• Target: 33
• Locations: 0 countries
• Sites: N/A

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

Keywords

Lymphoma; AMG 655; Trail receptor; Apoptosis; Vorinostat; Bortezomib; SAHA; Velcade

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (9)

• Part 2: Overall survival (OS).

  Length of study.

• Part 2: Progression-Free Survival (PFS).

  Length of treatment phase.

• Part 2: PK parameters for AMG 655 on a 3 week dosing schedule.

  Treatment and follow up phase of study.

• Part 2: Subject incidence of anti-AMG 655 antibody formation.

  Treatment and follow up phase of study.

• Part 2: Duration of response.

  Length of treatment phase.

Study Arms (7)

Cohort 4

EXPERIMENTAL

AMG 655 (intermediate dose) with Vorinostat

Drug: AMG 655; Other: Vorinostat

Cohort 1

EXPERIMENTAL

AMG 655 (low dose) with Bortezomib

Drug: AMG 655; Other: Bortezomib

Cohort 2

EXPERIMENTAL

AMG 655 (low dose) with vorinostat

Drug: AMG 655; Other: Vorinostat

Cohort 5

EXPERIMENTAL

AMG 655 (high dose) with Bortezomib

Drug: AMG 655; Other: Bortezomib

Cohort 6

EXPERIMENTAL

AMG 655 (high dose) with Vorinostat

Drug: AMG 655; Other: Vorinostat

Cohort 7

EXPERIMENTAL

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

Drug: AMG 655; Other: Bortezomib

Cohort 3

EXPERIMENTAL

AMG 655 (intermediate dose) with Bortezomib

Drug: AMG 655; Other: Bortezomib

Interventions

AMG 655 DRUG

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

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7

Vorinostat OTHER

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

Also known as: SAHA

Cohort 2; Cohort 4; Cohort 6

Bortezomib OTHER

A dipeptide boronic acid analogue with antineoplastic activity.

Also known as: Velcade

Cohort 1; Cohort 3; Cohort 5; Cohort 7

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Related 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;

  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;

  BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse

Interventions

conatumumab; Vorinostat; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2008
• First Posted: November 14, 2008
• Study Start: February 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: August 1, 2011
• Last Updated: March 5, 2014

Record last verified: 2014-03