Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated High- or High-Intermediate-Risk Diffuse Large B-Cell Lymphoma

NCT ID: NCT01539174

Last Updated: 2016-03-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Brief Summary

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This phase II trial studies how well giving rituximab together with combination chemotherapy works in treating patients with previously untreated high- or high-intermediate-risk diffuse large B-cell lymphoma (DLBCL). Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug, combination chemotherapy, may kill more cancer cells. Giving rituximab together with combination chemotherapy together may be an effective treatment for DLBCL

Detailed Description

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PRIMARY OBJECTIVES:

I. To evaluate 1 year progression-free survival (PFS) following treatment with rituximab intense dosing and CHOP-21 (RID-CHOP) in previously untreated patients with high risk (International Prognostic Index \[IPI\] 3-5) DLBCL.

SECONDARY OBJECTIVES:

I. To evaluate, in previously untreated patients with high risk (IPI 3-5) DLBCL treated with rituximab intense dosing and CHOP-21: Complete response (CR) rate, (as defined by International Harmonization Project criteria using 18-fluorodeoxyglucose \[FDG\] -positron emission tomography \[PET\]/computed tomography \[CT\]).

II. Overall survival.

III. Toxicity profile.

IV. Rituximab pharmacokinetics for this dose and schedule.

V. Effect of immunophenotype of DLBCL on outcome.

VI. Effect of Fc-Gamma Receptor III (FcyRIII) polymorphism genotype on outcome. OUTLINE: Patients receive rituximab intravenously (IV) on days 0, 1, 4, 8, and 15 of course 1; days 1, 8, and 15 of course 2; and day 1 of all subsequent courses. Patients also receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone orally (PO) on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2-3 months for 2 years, every 6 months for 3 years, annually for up to 10 years.

Conditions

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Contiguous Stage II Adult Diffuse Large Cell Lymphoma Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma Stage I Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (monoclonal antibody, combination chemotherapy)

Patients receive rituximab IV on days 0, 1, 4, 8, and 15 of course 1; days 1, 8, and 15 of course 2; and day 1 of all subsequent courses. Patients also receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

rituximab

Intervention Type BIOLOGICAL

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

vincristine sulfate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given PO

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

pharmacological study

Intervention Type OTHER

Correlative studies

Interventions

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rituximab

Given IV

Intervention Type BIOLOGICAL

cyclophosphamide

Given IV

Intervention Type DRUG

doxorubicin hydrochloride

Given IV

Intervention Type DRUG

vincristine sulfate

Given IV

Intervention Type DRUG

prednisone

Given PO

Intervention Type DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

pharmacological study

Correlative studies

Intervention Type OTHER

Other Intervention Names

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IDEC-C2B8 IDEC-C2B8 monoclonal antibody Mabthera MOAB IDEC-C2B8 Rituxan CPM CTX Cytoxan Endoxan Endoxana ADM ADR Adria Adriamycin PFS Adriamycin RDF leurocristine sulfate VCR Vincasar PFS DeCortin Deltra pharmacological studies

Eligibility Criteria

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Inclusion Criteria

* Newly diagnosed cluster of differentiation (CD) 20+ DLBCL with IPI between 3-5
* No prior chemotherapy, radiation therapy or immunotherapy for DLBCL; a short course (\< 2 weeks) of corticosteroids is allowed for symptom control Signed informed consent
* Eastern Cooperative Oncology Group (ECOG) Performance status assessed between 0 and 2; performance status of 3 will be accepted if impairment is caused by DLBCL complications and improvement is expected once therapy is initiated
* Measurable disease by Non-Hodgkin's Lymphoma Response Criteria on FDG-PET/CT; baseline measurements and evaluations must be obtained =\< 21 days prior to registration
* Absolute neutrophil count (ANC) \>= 1,500/μL unless due to marrow involvement by lymphoma
* Platelets \>= 75,000/μL unless due to marrow involvement by lymphoma Hemoglobin \> 7.0 g/dL unless due to marrow involvement by lymphoma
* Creatinine =\< 2.0 mg/dL or calculated creatinine clearance \>= 40
* Total bilirubin =\< 1.5 mg/dL unless due to Gilbert's disease
* Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =\< 2.5 the upper limit of normal
* Alkaline phosphatase =\< 5x upper limit of normal
* Patients with bilirubin between 1.5-3.0 mg/dL due to lymphoma may be entered and doses adjusted
* Left ventricular ejection fraction (LVEF) \>= 50%

Exclusion Criteria

* Women who are pregnant or breast feeding
* Known seropositivity for human immunodeficiency virus (HIV)
* Known presence of central nervous system (CNS) involvement by lymphoma
* New York Heart Association Classification III or IV heart
* Current or chronic hepatitis B or hepatitis C infection (as detected by positive testing for Hepatitis B surface Antigen \[Hbs Ag\] or antibody to Hepatitis C virus \[anti HCV\] respectively); patients must be tested for Hepatitis B surface antigen and anti-HCV =\< 21 days prior to registration
* Male patients (with female sexual partners of childbearing potential) and female patients of childbearing potential who refuse to use effective methods of contraception
* Unstable or severe uncontrolled medical, psychological, or social condition
* Any evidence of serious active, uncontrolled infection (i.e., requiring an IV antibiotic or antiviral agent)
* Receipt of live vaccine within 4 weeks prior to study drug administration
* Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix; subjects with previous malignancies are eligible provided that they have been treated with curative intent and remain disease free for 3 years or more
* No prior chemotherapy for lymphoma
* Prior radiation therapy for lymphoma
* Any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, significantly increase the subject's risk of participating in this study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Fox Chase Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Millenson, MD, FACP

Role: PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Locations

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Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2011-03309

Identifier Type: REGISTRY

Identifier Source: secondary_id

OER-HM-039

Identifier Type: -

Identifier Source: org_study_id

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