Clinical trial NCT00869323: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lymphoproliferative Disorder
Keywords: post-transplant lymphoproliferative disorder
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
Collaborators: name: Millennium Pharmaceuticals, Inc.
First posted: 2009-03-26
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Patients With Overall (Complete and Partial) Response Rates
timeFrame: Day 1 to 2 Years Post Treatment
Secondary outcomes:
measure: Remission Duration Among Patients Who Respond to Treatment
timeFrame: Day 1 to 8 Months Post Treatment
measure: Time to Treatment Failure
timeFrame: Day 1 to Time of Disease Progression
measure: Relapse-free Survival
timeFrame: at 2 years
measure: Overall Survival
timeFrame: at 2 years
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center - Fairview
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Oncology Division
state: Missouri
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Anne H. Blaes, MD
role: PRINCIPAL_INVESTIGATOR
References: