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

Phase 2
18 Years
Not Enrolling

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Trial Information

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



- 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.


- 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.

Inclusion Criteria


- 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


- 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

- 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


- 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

Type of Study:


Study Design:

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

Outcome Measure:

Antitumor efficacy in terms of overall, complete, and partial response rates and time to progression at weeks 9 and 21

Outcome Time Frame:

at weeks 9 and 21

Safety Issue:


Principal Investigator

Myron S. Czuczman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

January 2009

Completion Date:

September 2011

Related Keywords:

  • Lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • anaplastic large cell lymphoma
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse



Roswell Park Cancer Institute Buffalo, New York  14263