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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

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

Status
Terminated
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00851552
Enrollment
9
Registered
2009-02-26
Start date
2009-01-31
Completion date
2011-09-30
Last updated
2014-07-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma

Keywords

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

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.

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.

Interventions

BIOLOGICALrituximab

Given IV

DRUGbortezomib

Given IV

DRUGpegylated liposomal doxorubicin hydrochloride

Given IV

GENETICgene expression analysis

Correlative Study

GENETICpolymerase chain reaction

Correlative Study

GENETICpolymorphism analysis

Correlative Study

GENETICproteomic profiling

Correlative Study

OTHERflow cytometry

Correlative Study

OTHERlaboratory biomarker analysis

Correlative Study

Sponsors

Ortho Biotech, Inc.
CollaboratorINDUSTRY
Roswell Park Cancer Institute
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion 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

Design outcomes

Primary

MeasureTime frame
Antitumor Efficacy in Terms of Overall, Complete, and Partial Response Rates and Time to Progression at Weeks 9 and 21at weeks 9 and 21

Secondary

MeasureTime frame
Safety2 years

Countries

United States

Participant flow

Participants by arm

ArmCount
VDR: Velcade, Doxil, and Rituxan
VELCADE - 1.3mg/m2 IV, days 1, 4, 8, 11 every 21 days x 6 cycles DOXIL - 30 mg/m2 IV, day 11 every 21 days x 6 cycles RITUXAN - 375 mg/m2 IV, day 8 every 21 days x 6 cycles
9
Total9

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyAdverse Event1
Overall StudyDeath2
Overall StudyDisease Progression4

Baseline characteristics

CharacteristicVDR: Velcade, Doxil, and Rituxan
Age, Continuous61.78 years
STANDARD_DEVIATION 18.82
Sex: Female, Male
Female
5 Participants
Sex: Female, Male
Male
4 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
7 / 9
serious
Total, serious adverse events
5 / 9

Outcome results

Primary

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

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

Secondary

Safety

Time frame: 2 years

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

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026