Bortezomib and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorders

University of Minnesota (UMN)

Status and phase

Terminated

Phase 2

Conditions

Lymphoproliferative Disorder

Treatments

Biological: rituximab

Drug: bortezomib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00869323

2008LS043

MT2008-05R (Other Identifier)

0806M37121 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

3 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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