Bortezomib and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorders
Primary Purpose
Lymphoproliferative Disorder
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rituximab
bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoproliferative Disorder focused on measuring post-transplant lymphoproliferative disorder
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed CD20+ B-cell post-transplant lymphoproliferative disorder
- Has undergone prior solid organ transplant
- Measurable disease as defined by Non-Hodgkin Lymphoma Response Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) ≥ 1,000/mm³
- Platelet count ≥ 75,000/mm³
- Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 40 mL/min
- Alanine transaminase (ALT) and Aspartate aminotransferase (AST) ≤ 3 times upper limit of normal
- Total bilirubin ≤ 2.0 mg/dL
Exclusion Criteria:
- Pregnant or nursing
- Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- Peripheral neuropathy ≥ grade 2
- Known lymphomatous meningitis or central nervous system (CNS) involvement
- HIV infection
- Uncontrolled infection
- Myocardial infarction within the past 6 months or uncontrolled angina
- New York Heart Association class III-IV heart failure
- Severe uncontrolled ventricular arrhythmias
- Evidence of acute ischemia or active conduction system abnormalities by electrocardiogram (EKG)
- Concurrent serious medical or psychiatric disorder (e.g., active infection or uncontrolled diabetes) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study
- Diagnosis or treatment for another malignancy within the past 3 years, except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, in situ malignancy, or curatively treated low-risk prostate cancer
- Known hypersensitivity to rituximab, bortezomib, boron, or any of the other agents used in this study
- Less than 14 days since prior investigational drugs
- Less than 4 weeks since prior bortezomib therapy (12 weeks for rituximab) and recovered from toxic effects prior to enrollment
Sites / Locations
- University of Minnesota Medical Center - Fairview
- Washington University School of Medicine - Oncology Division
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treated Patients
Arm Description
This group includes patients receiving Bortezomib and Rituximab for post-transplant lymphoproliferative disorders (PTLD).
Outcomes
Primary Outcome Measures
Number of Patients With Overall (Complete and Partial) Response Rates
Secondary Outcome Measures
Remission Duration Among Patients Who Respond to Treatment
Time to Treatment Failure
Relapse-free Survival
Overall Survival
Full Information
NCT ID
NCT00869323
First Posted
March 25, 2009
Last Updated
December 3, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
Collaborators
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00869323
Brief Title
Bortezomib and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorders
Official Title
Phase II Trial of Bortezomib and Rituximab for Patients With Post Transplant Lymphoproliferative Disorders (PTLD)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Why Stopped
Funding unavailable
Study Start Date
March 2009 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
December 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota
Collaborators
Millennium Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Monoclonal antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with rituximab may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with rituximab works in treating patients with post-transplant lymphoproliferative disorders.
Detailed Description
OBJECTIVES:
Primary
To estimate the overall (complete and partial) response rates in patients with CD20+ post-transplant lymphoproliferative disorders treated with bortezomib and rituximab.
Secondary
To evaluate the duration of remission, time to treatment failure, relapse-free survival, and overall survival of these patients.
To characterize the quantitative and qualitative toxicities of this regimen.
OUTLINE:
Induction therapy: Patients receive bortezomib intravenously (IV) and rituximab IV on days 1, 8, 15, and 22.
Patients achieving complete remission (CR) after completion of induction therapy proceed to maintenance therapy after 6 months of rest. Patients achieving partial remission (PR) or stable disease after completion of induction therapy receive additional bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/PR after completion of bortezomib therapy proceed to maintenance therapy after 3 months of rest.
Maintenance therapy: Patients receive bortezomib IV and rituximab IV on days 1, 8, 15, and 22. Treatment repeats every 6 months for 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 2 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoproliferative Disorder
Keywords
post-transplant lymphoproliferative disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treated Patients
Arm Type
Experimental
Arm Description
This group includes patients receiving Bortezomib and Rituximab for post-transplant lymphoproliferative disorders (PTLD).
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
375 mg/m^2 intravenously on Days 1,8, 15 and 22
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
1.3 mg/m^2 intravenous bolus days 1, 8, 15 and 22
Primary Outcome Measure Information:
Title
Number of Patients With Overall (Complete and Partial) Response Rates
Time Frame
Day 1 to 2 Years Post Treatment
Secondary Outcome Measure Information:
Title
Remission Duration Among Patients Who Respond to Treatment
Time Frame
Day 1 to 8 Months Post Treatment
Title
Time to Treatment Failure
Time Frame
Day 1 to Time of Disease Progression
Title
Relapse-free Survival
Time Frame
at 2 years
Title
Overall Survival
Time Frame
at 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed CD20+ B-cell post-transplant lymphoproliferative disorder
Has undergone prior solid organ transplant
Measurable disease as defined by Non-Hodgkin Lymphoma Response Criteria
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count (ANC) ≥ 1,000/mm³
Platelet count ≥ 75,000/mm³
Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 40 mL/min
Alanine transaminase (ALT) and Aspartate aminotransferase (AST) ≤ 3 times upper limit of normal
Total bilirubin ≤ 2.0 mg/dL
Exclusion Criteria:
Pregnant or nursing
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
Peripheral neuropathy ≥ grade 2
Known lymphomatous meningitis or central nervous system (CNS) involvement
HIV infection
Uncontrolled infection
Myocardial infarction within the past 6 months or uncontrolled angina
New York Heart Association class III-IV heart failure
Severe uncontrolled ventricular arrhythmias
Evidence of acute ischemia or active conduction system abnormalities by electrocardiogram (EKG)
Concurrent serious medical or psychiatric disorder (e.g., active infection or uncontrolled diabetes) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study
Diagnosis or treatment for another malignancy within the past 3 years, except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, in situ malignancy, or curatively treated low-risk prostate cancer
Known hypersensitivity to rituximab, bortezomib, boron, or any of the other agents used in this study
Less than 14 days since prior investigational drugs
Less than 4 weeks since prior bortezomib therapy (12 weeks for rituximab) and recovered from toxic effects prior to enrollment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne H. Blaes, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota Medical Center - Fairview
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University School of Medicine - Oncology Division
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Bortezomib and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorders
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