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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00851552
Recruitment Status : Terminated (Lack of sponsor support)
First Posted : February 26, 2009
Results First Posted : July 21, 2014
Last Update Posted : July 21, 2014
Sponsor:
Collaborator:
Ortho Biotech, Inc.
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Drug: bortezomib Drug: pegylated liposomal doxorubicin hydrochloride Genetic: gene expression analysis Genetic: polymerase chain reaction Genetic: polymorphism analysis Genetic: proteomic profiling Other: flow cytometry Other: laboratory biomarker analysis Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of VDR (VELCADE™, DOXIL® and RITUXAN™) in Relapsed/Refractory Diffuse Large B-cell Lymphoma
Study Start Date : January 2009
Actual Primary Completion Date : September 2011
Actual Study Completion Date : September 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Intervention Details:
  • Biological: rituximab
    Given IV
  • Drug: bortezomib
    Given IV
  • Drug: pegylated liposomal doxorubicin hydrochloride
    Given IV
  • Genetic: gene expression analysis
    Correlative Study
  • Genetic: polymerase chain reaction
    Correlative Study
  • Genetic: polymorphism analysis
    Correlative Study
  • Genetic: proteomic profiling
    Correlative Study
  • Other: flow cytometry
    Correlative Study
  • Other: laboratory biomarker analysis
    Correlative Study

Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Safety [ Time Frame: 2 years ]

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

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
Contacts and Locations
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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): NCT00851552


Locations
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United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Ortho Biotech, Inc.
Investigators
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Principal Investigator: Myron S. Czuczman, MD Roswell Park Cancer Institute
More Information
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Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00851552    
Other Study ID Numbers: CDR0000635486
RPCI-I-136508
First Posted: February 26, 2009    Key Record Dates
Results First Posted: July 21, 2014
Last Update Posted: July 21, 2014
Last Verified: June 2014
Keywords provided by Roswell Park Cancer Institute:
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
anaplastic large cell lymphoma
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Rituximab
Doxorubicin
 Liposomal doxorubicin
Bortezomib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action