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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00869323
First received: March 25, 2009
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Lymphoproliferative Disorder
Biological: rituximab
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Bortezomib and Rituximab for Patients With Post Transplant Lymphoproliferative Disorders (PTLD)

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Number of Patients with Overall (complete and partial) response rates [ Time Frame: Day 1 to 2 Years Post Treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Remission duration among patients who respond to treatment [ Time Frame: Day 1 to 8 Months Post Treatment ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Day 1 to Time of Disease Progression ] [ Designated as safety issue: No ]
  • Relapse-free survival [ Time Frame: Day 1 to Time of Disease Progression ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Day 1 to Time of Death ] [ Designated as safety issue: No ]
  • Safety and toxicity [ Time Frame: Day 1 through 30 days post treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: March 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Rituxan
Drug: bortezomib
1.3 mg/m^2 intravenous bolus days 1, 8, 15 and 22
Other Name: Velcade

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00869323

Locations
United States, Minnesota
University of Minnesota Medical Center - Fairview
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University School of Medicine - Oncology Division
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Anne H. Blaes, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00869323     History of Changes
Other Study ID Numbers: 2008LS043, MT2008-05R, 0806M37121
Study First Received: March 25, 2009
Last Updated: June 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
post-transplant lymphoproliferative disorder

Additional relevant MeSH terms:
Disease
Lymphoproliferative Disorders
Pathologic Processes
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 16, 2014