NCT01686165

Brief Summary

This study looks at what effects (good and bad) a drug called PXD-101 (belinostat) in combination with the radioactive drug Zevalin (yttrium Y 90 ibritumomab tiuxetan) has on patients with relapsed aggressive (high-risk) non-Hodgkin lymphoma. Studies in the laboratory suggest that drugs such as PXD101 can act upon specific cancer cell processes to cause either death of the cancer cells or prevention of their growth. In human studies with a small number of patients with this lymphoma, PXD-101 has shown the ability to shrink and slow tumor growth. When Zevalin is delivered directly to the tumor, the lymphoma cells are destroyed and this may result in the disappearance of the tumor (remission)

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Aug 2012

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 31, 2012

Completed
12 days until next milestone

First Submitted

Initial submission to the registry

September 12, 2012

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 17, 2012

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 9, 2016

Completed
1.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 9, 2017

Completed
9 months until next milestone

Results Posted

Study results publicly available

July 31, 2018

Completed
Last Updated

August 28, 2018

Status Verified

July 1, 2018

Enrollment Period

3.4 years

First QC Date

September 12, 2012

Results QC Date

July 2, 2018

Last Update Submit

July 30, 2018

Conditions

Outcome Measures

Primary Outcomes (2)

  • Complete Response Rate

    To document the complete response rate for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma (NHL) treated with two cycles PXD-101 followed by one cycle of the Zevalin regimen.

    Up to 5 years

  • Overall Response

    To document the overall response for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma (NHL) treated with two cycles PXD-101 followed by one cycle of the Zevalin regimen.

    Up to 5 years

Secondary Outcomes (2)

  • Progression-free Survival

    2 years

  • Occurrence of Adverse Events and Serious Adverse Events

    Up to 30 days after patient receives last dose of study drug

Study Arms (1)

Belinostat Yttrium Ibritumomab Tiuxetan

EXPERIMENTAL

Patients receive belinostat IV over 30-60 minutes on days 1-5. Treatment with belinostat repeats every 21 days for 2 courses. Patients then receive rituximab IV on days 1 and either 7, 8, or 9, and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 50. Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: belinostatBiological: rituximabRadiation: yttrium Y 90 ibritumomab tiuxetan

Interventions

Given IV

Also known as: PXD101
Belinostat Yttrium Ibritumomab Tiuxetan
rituximabBIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Belinostat Yttrium Ibritumomab Tiuxetan

Given IV

Also known as: 90Y ibritumomab tiuxetan, IDEC Y2B8, Y90 Zevalin, Y90-labeled ibritumomab tiuxetan
Belinostat Yttrium Ibritumomab Tiuxetan

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Biopsy confirmed, CD20 positive diffuse large B-cell lymphoma, primary mediastinal b-cell lymphoma, mantel cell lymphoma, transformed indolent lymphoma, high grade-B-cell lymphoma; AND bone marrow must show =\< 20% CD20+ B-cells with \>= 15% cellularity within 42 days of study registration
  • Any stage disease
  • Patients must have been previously treated:
  • \>= 3rd line if bone marrow transplant (BMT) candidate OR
  • \>= 2nd line if not BMT candidate OR
  • \>= 2nd relapse for BMT candidate OR
  • \>= 1st relapse for non- BMT candidate
  • Must have a diagnostic quality CT scan of the chest, abdomen and pelvis OR baseline PET-CT scan performed within 28 days prior to registration
  • Must have bidimensionally measurable disease with lesions at least 1.5 cm in one dimension ALL measurable disease must be assessed within 28 days of registration
  • To determine prior drug regimens: radiation therapy counts as 1 treatment, BMT including induction counts as one treatment, radioimmunotherapy is not considered a chemotherapy regimen, rituximab alone is not considered a treatment; all prior therapy must have been completed at least 30 days prior to registration; patients should not have taken valproic acid, or any other histone deacetylase inhibitor (eg., vorinostat, romidepsin), for at least 30 days prior to registration; patients must have recovered from any toxicities related to therapies prior to registration
  • No clinical evidence of CNS involvement by lymphoma, any lab (eg., LDH or radiographic tests performed to access CNS involvement must be negative and must be performed within 42 days prior to registration
  • Unilateral or bilateral bone marrow biopsy performed within 42 days prior to registration
  • Life expectancy of greater than 3 months
  • Karnofsky performance status \>= 60%
  • Leukocytes \>= 3,000/mcL
  • +9 more criteria

You may not qualify if:

  • Patients who have had chemotherapy or radiotherapy within 30 days (6 weeks for nitrosoureas or mitomycin C) prior to study screening or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Prior radioimmunotherapy
  • Pregnant or nursing
  • Clinical evidence of CNS involvement by lymphoma
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD-101 or Zevalin or other agents used in the study
  • Concomitant medication that may cause Torsade de Pointes, i.e. prolongation of the QT interval \> 500 msec
  • Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure related to primary cardiac disease, any condition requiring anti-arrhythmic therapy, ischemic or valvular heart disease, or a myocardial infarction within the past 6 months
  • Current long QT syndrome or baseline prolongation of QT/QTcF interval, i.e. demonstration of a QTcF interval \> 450 msec
  • Clinical evidence of severe peripheral vascular disease, diabetic ulcers or venous stasis ulcers, or history of deep venous or arterial thrombosis within 3 months prior to screening
  • Known to be human immunodeficiency virus (HIV) positive or with known acquired immunodeficiency syndrome (AIDS) syndrome
  • Patients may not be receiving any other investigational agents

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Arizona Cancer Center

Tucson, Arizona, 85724-5024, United States

Location

Related Publications (1)

  • Puvvada SD, Guillen-Rodriguez JM, Rivera XI, Heard K, Inclan L, Schmelz M, Schatz JH, Persky DO. A Phase II Exploratory Study of PXD-101 (Belinostat) Followed by Zevalin in Patients with Relapsed Aggressive High-Risk Lymphoma. Oncology. 2017;93(6):401-405. doi: 10.1159/000479230. Epub 2017 Sep 5.

MeSH Terms

Conditions

Lymphoma, Large-Cell, AnaplasticLymphoma, Large B-Cell, DiffuseLymphoma, Mantle-Cell

Interventions

belinostatRituximabibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Lymphoma, T-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Daniel Persky, M.D.
Organization
University of Arizona Cancer Center

Study Officials

  • Daniel O. Persky, MD

    University of Arizona

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 12, 2012

First Posted

September 17, 2012

Study Start

August 31, 2012

Primary Completion

February 9, 2016

Study Completion

November 9, 2017

Last Updated

August 28, 2018

Results First Posted

July 31, 2018

Record last verified: 2018-07

Locations