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

Phase II Trial of Bortezomib and Rituximab for Patients With Post Transplant Lymphoproliferative Disorders (PTLD)

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.

Study Overview

• Status: Terminated
• Conditions: Lymphoproliferative Disorder
• Intervention / Treatment: Biological: rituximab; Drug: bortezomib

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center - Fairview
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine - Oncology Division

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treated Patients; This group includes patients receiving Bortezomib and Rituximab for post-transplant lymphoproliferative disorders (PTLD).	Biological: rituximab; 375 mg/m^2 intravenously on Days 1,8, 15 and 22; Other Names: Rituxan; Drug: bortezomib; 1.3 mg/m^2 intravenous bolus days 1, 8, 15 and 22; Other Names: Velcade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Patients With Overall (Complete and Partial) Response Rates	Day 1 to 2 Years Post Treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Relapse-free Survival	at 2 years
Remission Duration Among Patients Who Respond to Treatment	Day 1 to 8 Months Post Treatment
Time to Treatment Failure	Day 1 to Time of Disease Progression
Overall Survival	at 2 years

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Collaborators: Millennium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: March 25, 2009
• First Submitted That Met QC Criteria: March 25, 2009
• First Posted (Estimate): March 26, 2009

Study Record Updates

• Last Update Posted (Actual): December 5, 2017
• Last Update Submitted That Met QC Criteria: December 3, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: post-transplant lymphoproliferative disorder
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Disease; Lymphoproliferative Disorders; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab; Bortezomib
• Other Study ID Numbers: 2008LS043; MT2008-05R (Other Identifier: Blood and Marrow Transplantation Program); 0806M37121 (Other Identifier: IRB, University of Minnesota)