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

Information source: Amgen
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hodgkin's Lymphoma; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Diffuse Large Cell Lymphoma

Intervention: AMG 655 (Drug); Vorinostat (Other); Bortezomib (Other)

Phase: Phase 1

Status: Completed

Sponsored by: Amgen

Official(s) and/or principal investigator(s):
MD, Study Director, Affiliation: Amgen

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.

Clinical Details

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

Primary outcome:

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:

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Additional Information

AmgenTrials clinical trials website

Related publications:

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;

Starting date: February 2008
Last updated: March 3, 2014

Page last updated: August 23, 2015

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