Hodgkin's LymphomaPhase 1NCT00791011
Phase 1b Lymphoma Study of AMG 655 in Combination With Bortezomib or Vorinostat
A Phase 1 study testing AMG 655, Vorinostat and Bortezomib in people with Hodgkin's Lymphoma and Low Grade Lymphoma, run by Amgen.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin's Lymphoma, Low Grade Lymphoma, Lymphoma
- What is being tested?
- AMG 655, Vorinostat and Bortezomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- No sites listed yet
- Study dates
- Feb 2008to Aug 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
About this study
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
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
- Being tested
- AMG 655, Vorinostat, Bortezomib
- Keywords
- Lymphoma, AMG 655, Trail receptor, Apoptosis, Vorinostat, Bortezomib, SAHA, Velcade
- Medical subject headings
- Hodgkin Disease, Lymphoma, Non-Hodgkin, Lymphoma, Lymphoma, Mantle-Cell, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 655Drug
AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5).
VorinostatOther
Also called SAHA
Vorinostat, a second generation polarplanar compound, binds to the catalytic domain of the histone deacetylases (HDAC).
BortezomibOther
Also called Velcade
A dipeptide boronic acid analogue with antineoplastic activity.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 4 | Experimental | AMG 655 (intermediate dose) with Vorinostat Receives: Drug: AMG 655; Other: Vorinostat |
| Cohort 1 | Experimental | AMG 655 (low dose) with Bortezomib Receives: Drug: AMG 655; Other: Bortezomib |
| Cohort 2 | Experimental | AMG 655 (low dose) with vorinostat Receives: Drug: AMG 655; Other: Vorinostat |
| Cohort 5 | Experimental | AMG 655 (high dose) with Bortezomib Receives: Drug: AMG 655; Other: Bortezomib |
| Cohort 6 | Experimental | AMG 655 (high dose) with Vorinostat Receives: Drug: AMG 655; Other: Vorinostat |
| Cohort 7 | Experimental | Part 2 - Mantle Cell Lymphoma subjects only: AMG 655 at dose TBD with Bortezomib Receives: Drug: AMG 655; Other: Bortezomib |
| Cohort 3 | Experimental | AMG 655 (intermediate dose) with Bortezomib Receives: Drug: AMG 655; Other: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: Length of Study
Secondary outcomes (9)
Part 2: Overall survival (OS).
Measured: Length of study.
Part 2: Progression-Free Survival (PFS).
Measured: Length of treatment phase.
Part 2: PK parameters for AMG 655 on a 3 week dosing schedule.
Measured: Treatment and follow up phase of study.
Part 2: Subject incidence of anti-AMG 655 antibody formation.
Measured: Treatment and follow up phase of study.
Part 2: Duration of response.
Measured: Length of treatment phase.
Part 1: Subject incidence of anti-AMG 655 antibody formation.
Measured: Treatment and follow up phase of study.
Part 1: Best tumor response, objective response rate and duration of response.
Measured: Length of treatment phase.
Part 1: Maximum tolerated dose of AMG 655 administered with bortezomib or vorinostat, if reached.
Measured: First 21 days of treatment for each cohort.
Part 1: PK parameters for AMG 655 on a 3 week dosing schedule.
Measured: Treatment and follow up phase of study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2008 (estimated)
- Study startFeb 2008
- Primary completionJul 2010
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00791011
- Sponsor's protocol ID
- 20060340
- Status last verified
- Mar 2014
- First submitted
- 13 Nov 2008
- Last updated
- 5 Mar 2014
- Results posted
- No
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;
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00791011
- Acronym / sponsor ID
- 20060340
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- Feb 2008
- Primary completion
- Jul 2010 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 14 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort 4 | Experimental | Drug: AMG 655, Other: VorinostatAMG 655 (intermediate dose) with Vorinostat |
| Cohort 1 | Experimental | Drug: AMG 655, Other: BortezomibAMG 655 (low dose) with Bortezomib |
| Cohort 2 | Experimental | Drug: AMG 655, Other: VorinostatAMG 655 (low dose) with vorinostat |
| Cohort 5 | Experimental | Drug: AMG 655, Other: BortezomibAMG 655 (high dose) with Bortezomib |
| Cohort 6 | Experimental | Drug: AMG 655, Other: VorinostatAMG 655 (high dose) with Vorinostat |
| Cohort 7 | Experimental | Drug: AMG 655, Other: BortezomibPart 2 - Mantle Cell Lymphoma subjects only: AMG 655 at dose TBD with Bortezomib |
| Cohort 3 | Experimental | Drug: AMG 655, Other: BortezomibAMG 655 (intermediate dose) with Bortezomib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 655AMG 655 is an investigational, fully human monoclonal agonist antibidy that selectively binds to Death Receptor-5 (DR-5). | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6, Cohort 7 |
| VorinostatAlso: SAHAVorinostat, a second generation polarplanar compound, binds to the catalytic domain of the histone deacetylases (HDAC). | Other | Cohort 2, Cohort 4, Cohort 6 |
| BortezomibAlso: VelcadeA dipeptide boronic acid analogue with antineoplastic activity. | Other | Cohort 1, Cohort 3, Cohort 5, Cohort 7 |
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.
Time frame: 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
Time frame: Length of Study
9 secondary outcomes
Part 2: Overall survival (OS).
Time frame: Length of study.
Part 2: Progression-Free Survival (PFS).
Time frame: Length of treatment phase.
Part 2: PK parameters for AMG 655 on a 3 week dosing schedule.
Time frame: Treatment and follow up phase of study.
Part 2: Subject incidence of anti-AMG 655 antibody formation.
Time frame: Treatment and follow up phase of study.
Part 2: Duration of response.
Time frame: Length of treatment phase.
Part 1: Subject incidence of anti-AMG 655 antibody formation.
Time frame: Treatment and follow up phase of study.
Part 1: Best tumor response, objective response rate and duration of response.
Time frame: Length of treatment phase.
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.
Part 1: PK parameters for AMG 655 on a 3 week dosing schedule.
Time frame: Treatment and follow up phase of study.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2014.
- BackgroundYounes 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;
- BackgroundYounes 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;
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 655, Vorinostat and Bortezomib in people with Hodgkin's Lymphoma and Low Grade Lymphoma, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Length of Study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00791011, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2014.