Bortezomib Plus Rituximab for EBV+ PTLD

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Massachusetts General Hospital
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Jeremy Abramson, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01058239
First received: January 26, 2010
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bortezomib Plus Rituximab for EBV + Post Transplant Lymphoproliferative Disease (PTLD)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Overall response rate includes both complete and partial responses assessed by PET/CT following completion of therapy


Secondary Outcome Measures:
  • progression-free survival and overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • safety of bortezomib with rituximab [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To evaluate effects of bortezomib/rituximab on EBV quantitative viral load [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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: NCT01058239

Contacts
Contact: Jeremy Abramson, MD 617-726-8743 jabramson@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Jeremy Abramson, MD         
Dana-Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Ann LaCasce, MD         
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Robin Joyce, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Jeremy Abramson, MD Massachusetts General Hospital
  More Information

No publications provided

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
Study First Received: January 26, 2010
Last Updated: May 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
bortezomib
rituximab
PTLD
EBV
transplantation

Additional relevant MeSH terms:
Epstein-Barr Virus Infections
Virus Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections
Neoplasms, Experimental
Neoplasms
Rituximab
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 22, 2014