Bortezomib, Doxorubicin Hydrochloride Liposome, and Rituximab in Treating Patients With Diffuse Large B-Cell Lymphoma That Has Relapsed or Not Responded to Treatment

June 23, 2014 updated by: Roswell Park Cancer Institute

A Phase II Study of VDR (VELCADE™, DOXIL® and RITUXAN™) in Relapsed/Refractory Diffuse Large B-cell Lymphoma

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. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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 cell-killing substances to them. Giving bortezomib together with doxorubicin hydrochloride liposome and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with doxorubicin hydrochloride liposome and rituximab works in treating patients with diffuse large B-Cell lymphoma that has relapsed or not responded to treatment.

Study Overview

Status

Terminated

Conditions

Lymphoma

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

To determine the overall objective response rate (i.e., complete and partial response) in patients with relapsed or refractory, CD20-positive, diffuse large B-cell lymphoma treated with bortezomib, pegylated liposomal doxorubicin hydrochloride, and rituximab.

Secondary

To assess the toxicity/safety profile associated with this regimen.
To conduct correlative translational research studies.

OUTLINE: Patients receive bortezomib IV on days 1, 4, 8, and 11, pegylated liposomal doxorubicin hydrochloride IV on day 11, and rituximab IV on day 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Tissue and blood samples are collected periodically for correlative studies. Samples are analyzed for expression of CD11b/CD18, CD32, CD 33, CD62, CD64, CD69, and CD56 by flow cytometric analysis of neutrophils, NK cells, and monocytes; antibody-dependent cellular and complement-mediated cytotoxicity; and genotypic analysis of polymorphisms by PCR. Autologous neoplastic B-cells derived from tissue samples are used for genetic and protein profiling.

After completion of study therapy, patients are followed periodically for 4 years.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- New York
  - Buffalo, New York, United States, 14263-0001
    - Roswell Park Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Diagnosis of CD20-positive diffuse large B-cell lymphoma, including any of the following morphological variants:
- Centroblastic
- Immunoblastic
- T-cell/histiocyte-rich
- Anaplastic
- Mediastinal (thymic) large B-cell lymphoma
- Intravascular large B-cell lymphoma
Relapsed or refractory disease
Measurable disease, defined as tumor size 2 cm²
Must have received ≥ 1 prior standard chemotherapy regimen
No Burkitt or precursor B-lymphoblastic lymphoma
No brain involvement or evidence of CNS lymphoma

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 70-100% OR ECOG PS 0-2
Life expectancy ≥ 12 weeks
Absolute neutrophil count ≥ 1,500/μL*
Platelet count ≥ 100,000/μL*
Creatinine < 2.5 mg/dL OR > 40 mL/min*
Hemoglobin > 8.0 g/dL*
AST/ALT < 2 times upper limit of normal (ULN) (< 3 times ULN with liver involvement)*
Alkaline phosphatase < 2 times ULN (< 3 times ULN with liver involvement)*
Total bilirubin < 2 times ULN (< 3 times ULN with liver involvement or Gilbert disease)* NOTE: *Unless attributable to non-Hodgkin lymphoma
LVEF ≥ 50% by MUGA scan or ECHO
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after completion of therapy
No HIV positivity
No hepatitis B positivity
Peripheral neuropathy < grade 2 as defined by NCI CTCAE v 3.0
No history of uncontrolled orthostatic hypotension
None of the following cardiac conditions:
- Myocardial infarction within the past 6 months
- New York Heart Association class II-IV congestive heart failure
- Uncontrolled angina
- Severe uncontrolled ventricular arrhythmias
- Clinically significant pericardial disease
- ECG evidence of acute ischemic or active conduction system abnormalities
No hypersensitivity to bortezomib, boron, or mannitol
No history of allergic reactions to compounds containing boron, mannitol, bortezomib, conventional formulation of doxorubicin hydrochloride, or the components of pegylated liposomal doxorubicin hydrochloride
No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Poorly controlled hypertension
- Diabetes mellitus
- Serious medical or psychiatric conditions that would interfere with adherence to or completion of this study
No other primary malignancy except squamous cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, superficial bladder carcinoma, or previously treated localized prostate cancer with normal PSA levels and disease-free for ≥ 5 years

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from significant toxicity associated with prior surgery, radiotherapy, chemotherapy, or immunotherapy
Prior rituximab or other monoclonal immunotherapy allowed
More than 4 weeks since prior investigational drugs
More than 4 weeks since prior chemotherapy
More than 4 weeks since prior major surgery, other than diagnostic surgery
No prior doxorubicin hydrochloride (or equivalent) anthracycline treatment exceeding 400 mg/m²
No concurrent corticosteroids, except to control a transient inflammatory reaction (i.e., skin rash or hives)
- Concurrent non-steroidal hormones administered for non-lymphoma related conditions (e.g., insulin for diabetes) allowed
No concurrent radiotherapy
No other concurrent antitumor or chemotherapeutic agents
No other concurrent investigational agents

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Antitumor Efficacy in Terms of Overall, Complete, and Partial Response Rates and Time to Progression at Weeks 9 and 21 Time Frame: at weeks 9 and 21	at weeks 9 and 21

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety Time Frame: 2 years	2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Roswell Park Cancer Institute

Collaborators

Ortho Biotech, Inc.

Investigators

Principal Investigator: Myron S. Czuczman, MD, Roswell Park Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

September 1, 2011

Study Completion (Actual)