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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00851552
• Other study ID #: CDR0000635486
• Secondary ID: RPCI-I-136508
• Status: Terminated
• Phase: Phase 2
• First received: February 25, 2009
• Last updated: June 23, 2014
• Start date: January 2009
• Est. completion date: September 2011

Study information

• Verified date: June 2014
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Biological:
• rituximab
Given IV

Drug:
• bortezomib
Given IV
• pegylated liposomal doxorubicin hydrochloride
Given IV

Genetic:
• gene expression analysis
Correlative Study
• polymerase chain reaction
Correlative Study
• polymorphism analysis
Correlative Study
• proteomic profiling
Correlative Study

Other:
• flow cytometry
Correlative Study
• laboratory biomarker analysis
Correlative Study

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	Ortho Biotech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antitumor Efficacy in Terms of Overall, Complete, and Partial Response Rates and Time to Progression at Weeks 9 and 21		at weeks 9 and 21	No
Secondary	Safety		2 years	Yes