Belinostat and Yttrium Y 90 Ibritumomab Tiuxetan in Patients W/Relapsed Aggressive B-Cell NHL
Primary Purpose
Anaplastic Large Cell Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Mantle Cell Lymphoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
belinostat
rituximab
yttrium Y 90 ibritumomab tiuxetan
Sponsored by
About this trial
This is an interventional treatment trial for Anaplastic Large Cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
- 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
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- AST (SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
- Total bilirubin =< 1.5 X institutional upper limit of normal (unless associated with Gilbert's syndrome)
- Serum creatinine < 2 x institutional upper limit of normal OR
- Measured creatinine clearance >= 60 mL/min
- LDH < 1.50 X institutional upper limit of normal
- EKG with no significant abnormalities within 28 days prior to registration
- Women of child-bearing potential and men must agree to use adequate contraception
Exclusion Criteria:
- 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
Sites / Locations
- University of Arizona Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Belinostat Yttrium Ibritumomab Tiuxetan
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Progression-free Survival
Will be estimated using a Kaplan-Meier estimate. The observed 2-year progression-free survival rate will be estimated (with a 95% confidence interval) from the Kaplan-Meier curve.
Occurrence of Adverse Events and Serious Adverse Events
The proportion of patients with a given adverse event will be tabulated and the 95% confidence interval computed.
Full Information
NCT ID
NCT01686165
First Posted
September 12, 2012
Last Updated
July 30, 2018
Sponsor
University of Arizona
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01686165
Brief Title
Belinostat and Yttrium Y 90 Ibritumomab Tiuxetan in Patients W/Relapsed Aggressive B-Cell NHL
Official Title
A Phase II Exploratory Study of PXD-101(Belinostat) Followed by Zevalin in Patients With Relapsed Aggressive High-Risk Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
August 31, 2012 (Actual)
Primary Completion Date
February 9, 2016 (Actual)
Study Completion Date
November 9, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arizona
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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)
Detailed Description
PRIMARY OBJECTIVES:
I. To document the complete response rate and overall response for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma treated with two cycles PXD-101 followed by one cycle of Zevalin.
SECONDARY OBJECTIVES:
I. To estimate 2-year progression-free survival in patients with relapsed aggressive high-risk non-Hodgkin's lymphoma treated with two cycles PXD-101 followed by one cycle of Zevalin.
II. To evaluate the toxicity of two cycles PXD-101 and one cycle of Zevalin in patients with relapsed aggressive high-risk non-Hodgkin's lymphoma.
OUTLINE:
Patients receive belinostat intravenously (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.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anaplastic Large Cell Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Mantle Cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Belinostat Yttrium Ibritumomab Tiuxetan
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
belinostat
Other Intervention Name(s)
PXD101
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 ibritumomab tiuxetan
Other Intervention Name(s)
90Y ibritumomab tiuxetan, IDEC Y2B8, Y90 Zevalin, Y90-labeled ibritumomab tiuxetan
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Complete Response Rate
Description
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.
Time Frame
Up to 5 years
Title
Overall Response
Description
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.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
Will be estimated using a Kaplan-Meier estimate. The observed 2-year progression-free survival rate will be estimated (with a 95% confidence interval) from the Kaplan-Meier curve.
Time Frame
2 years
Title
Occurrence of Adverse Events and Serious Adverse Events
Description
The proportion of patients with a given adverse event will be tabulated and the 95% confidence interval computed.
Time Frame
Up to 30 days after patient receives last dose of study drug
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Absolute neutrophil count >= 1,500/mcL
Platelets >= 100,000/mcL
AST (SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
Total bilirubin =< 1.5 X institutional upper limit of normal (unless associated with Gilbert's syndrome)
Serum creatinine < 2 x institutional upper limit of normal OR
Measured creatinine clearance >= 60 mL/min
LDH < 1.50 X institutional upper limit of normal
EKG with no significant abnormalities within 28 days prior to registration
Women of child-bearing potential and men must agree to use adequate contraception
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel O. Persky, MD
Organizational Affiliation
University of Arizona
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724-5024
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28869931
Citation
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.
Results Reference
derived
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Belinostat and Yttrium Y 90 Ibritumomab Tiuxetan in Patients W/Relapsed Aggressive B-Cell NHL
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