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Bortezomib Plus Rituximab for EBV+ PTLD

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ClinicalTrials.gov Identifier: NCT01058239
Recruitment Status : Active, not recruiting
First Posted : January 28, 2010
Last Update Posted : June 20, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
Post transplant lymphoproliferative disease (PTLD) is a type of B-cell non-Hodgkin lymphoma that occurs in patients with weakened immune systems due to immunosuppressive medications taken after organ or stem cell transplantation. This is usually related to a virus called Epstein-Barr (EPV). Rituximab is a type of drug called an "antibody" that specifically destroys both normal and cancerous B-cells, and is commonly used for PTLD. Bortezomib is a drug that has been approved by the Food and Drug Administration (FDA) to treat multiple myeloma and a B-cell non-Hodgkin lymphoma called Mantle Cell Lymphoma, and shows significant activity in lymphoma cells caused by EBV. In this research study, we hope to learn if the addition of bortezomib to rituximab treatment can increase the rate of complete remissions and cures of PTLD after organ or stem cell transplant.

Condition or disease Intervention/treatment Phase
Post-transplant Lymphoproliferative Disease Solid Organ Transplant Stem Cell Transplant (Bone Marrow Transplant) Epstein Barr Virus Infections Drug: bortezomib Drug: rituximab Phase 2

Detailed Description:
  • Both rituximab and bortezomib will be given to participants intravenously. Each cycle of treatment will consist of 21 days. Rituximab will be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles. Bortezomib will be given on Days 1, 4, 8 and 11 of every cycle. Participants will receive a maximum of 4 cycles.
  • The following study procedures will be performed during each cycle throughout the study: Medical history review; Physical exam; Performance Status; Questionnaire; Blood draws and; PET/CT scans (After cycles 2, 4 and 6 only).
  • After Cycle 4, if the study doctor feels the participant has had a complete response to treatment, then they will continue onto the Post-Treatment Surveillance period, which will consist of regular clinic visits over two years.
  • However, if the study doctor feels the participant has had a partial response to treatment and that they may benefit from continuing, they will receive an additional two cycles of bortezomib and be given daily tablets of the antiviral drug valganciclovir to help further target EBV.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bortezomib Plus Rituximab for EBV + Post Transplant Lymphoproliferative Disease (PTLD)
Study Start Date : November 2011
Primary Completion Date : December 2016
Estimated Study Completion Date : December 2017

Arms and Interventions

Arm Intervention/treatment
Experimental: Rituximab plus Bortezomib
This is a single arm trial adding the new drug bortezomib to the standard drug rituximab
Drug: bortezomib
Given intravenously on days 1, 4, 8 and 11 of every cycle
Other Name: Velcade
Drug: rituximab
given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Other Names:
  • Rituxan
  • Mabthera

Outcome Measures

Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 4 months ]
    Overall response rate includes both complete and partial responses assessed by PET/CT following completion of therapy

Secondary Outcome Measures :
  1. progression-free survival and overall survival [ Time Frame: 3 years ]
  2. safety of bortezomib with rituximab [ Time Frame: 2 years ]
  3. To evaluate effects of bortezomib/rituximab on EBV quantitative viral load [ Time Frame: 2 years ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have had a prior solid organ or allogeneic stem cell transplant.
  • Patients may be newly-diagnosed or relapsed after prior therapy
  • Patients must have histologically confirmed CD20+ B-cell PTLD diagnosed according to WHO criteria. PTLD may be characterized as early lesions, PTLD/polymorphic, PTLD/monomorphic, or PTLD/other, all of which are eligible for this trial. B-cell PTLD must be associated with EBV as demonstrated either by detection of EBV antigens in tumor samples, or by increased EBV quantitative viral load in serum.
  • Patients must have measurable disease
  • 18 years of age or older
  • Estimated life expectancy of > 3 months
  • ECOG Performance status of 0, 1, or 2
  • Adequate organ and marrow function
  • Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.

Exclusion Criteria:

  • Patients receiving any other study agents. Patients already on prophylactic doses of ganciclovir or valganciclovir because of a prior history of CMV infection or because of risk factors for CMV infection are eligible for the study and may continue CMV prophylaxis.
  • Patients with known brain metastases or central nervous system (CNS) involvement of their lymphoma.
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib, rituximab, ganciclovir or valgancyclovir.
  • Patients with Grade 2 or greater neuropathy within 14 days before enrollment.
  • Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or breastfeeding women
  • Individuals with a history of malignancy are ineligible except for those outlined in the protocol
  • Known HIV positive individuals
  • Active HBV infection may be included only if they are on appropriate anti-hepatitis B therapy and have an undetectable HBV viral load
  • Patient has received other investigational drugs within 14 days before enrollment
  • Prior bortezomib
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01058239

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Millennium Pharmaceuticals, Inc.
Principal Investigator: Jeremy Abramson, MD Massachusetts General Hospital
More Information

Responsible Party: Jeremy Abramson, MD, Director, Lymphoma Program, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01058239     History of Changes
Other Study ID Numbers: 09-346
X05289 ( Other Identifier: Millennium )
First Posted: January 28, 2010    Key Record Dates
Last Update Posted: June 20, 2017
Last Verified: June 2017

Keywords provided by Jeremy Abramson, MD, Massachusetts General Hospital:

Additional relevant MeSH terms:
Virus Diseases
Lymphoproliferative Disorders
Epstein-Barr Virus Infections
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents