Bortezomib Plus Rituximab for EBV+ PTLD

NCT01058239 | Completed Phase 2 Results DMC

• 2 other identifiers: 09-346X05289
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

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.

Conditions

Post-transplant Lymphoproliferative Disease; Solid Organ Transplant; Stem Cell Transplant (Bone Marrow Transplant); Epstein Barr Virus Infections

Keywords

bortezomib; rituximab; PTLD; EBV; transplantation

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall response rate includes both complete and partial responses assessed by PET/CT following completion of therapy. Response was evaluated using the International Working Group criteria for lymphoma response. The complete list of criteria used to evaluate response is too long to be detailed in the allotted space here, but response is defined more generally as: * Complete Response (CR): Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. * Partial Response (PR): ≥ 50% decrease in the sum of the products of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses.

  4 months

Secondary Outcomes (5)

• Complete Response Rate

  4 Months

• Six-Month Progression Free Survival

  six months

• Overall Survival

  6 months, 1 year

• Effects of Bortezomib/Rituximab on EBV Quantitative Viral Load

  baseline, 21, 42, 63, 84 days (end of cycles 1, 2, 3, 4)

• Treatment Related Toxicities

  2 years

Study Arms (1)

Rituximab plus Bortezomib

EXPERIMENTAL

This is a single arm trial adding the new drug bortezomib to the standard drug rituximab

Drug: bortezomib; Drug: rituximab

Interventions

bortezomib DRUG

Given intravenously on days 1, 4, 8 and 11 of every cycle

Also known as: Velcade

Rituximab plus Bortezomib

rituximab DRUG

given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles

Also known as: Rituxan, Mabthera

Rituximab plus Bortezomib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• Brigham and Women's Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Epstein-Barr Virus Infections

Interventions

Bortezomib; Rituximab

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jeremy Abramson, M.D
• Organization: Massachusetts General Hospital

JABRAMSON@mgh.harvard.edu

617-724-4000

Study Officials

• Jeremy Abramson, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Lymphoma Program

Study Record Dates

• First Submitted: January 26, 2010
• First Posted: January 28, 2010
• Study Start: November 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: November 1, 2017
• Last Updated: February 15, 2018
• Results First Posted: February 15, 2018

Record last verified: 2018-01

Locations

US (3)