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

NCT00851552 | Terminated Phase 2 Results DMC

• 2 other identifiers: CDR0000635486RPCI-I-136508
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma

Keywords

recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; anaplastic large cell lymphoma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Safety

  2 years

Interventions

rituximab BIOLOGICAL

Given IV

bortezomib DRUG

Given IV

pegylated liposomal doxorubicin hydrochloride DRUG

Given IV

gene expression analysis GENETIC

Correlative Study

polymerase chain reaction GENETIC

Correlative Study

polymorphism analysis GENETIC

Correlative Study

proteomic profiling GENETIC

Correlative Study

flow cytometry OTHER

Correlative Study

laboratory biomarker analysis OTHER

Correlative Study

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Ortho Biotech, Inc.: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Large-Cell, Anaplastic

Interventions

Rituximab; Bortezomib; Gene Expression Profiling; Polymerase Chain Reaction; Amplified Fragment Length Polymorphism Analysis; Flow Cytometry

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Genetic Techniques; Investigative Techniques; Nucleic Acid Amplification Techniques; DNA Fingerprinting; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical

Limitations and Caveats

Due to the study's early termination and inadequate number of patients, no patients were analyzed.

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

716-845-2300

Study Officials

• Myron S. Czuczman, MD

  Roswell Park Cancer Institute

  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: SPONSOR

Study Record Dates

• First Submitted: February 25, 2009
• First Posted: February 26, 2009
• Study Start: January 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: July 21, 2014
• Results First Posted: July 21, 2014

Record last verified: 2014-06

Locations

US (1)