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

March 1, 2016 updated by: Fox Chase Cancer Center

A Phase II Study of Rituximab Intense Dosing With CHOP-21 (RID-CHOP) in Patients With Previously Untreated High or High-Intermediate Risk IPI (3-5) Diffuse Large B-Cell Lymphoma (DLBCL)

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

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: laboratory biomarker analysis
Correlative studies
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • Adriamycin PFS
  • Adriamycin RDF
  • ADR
  • Adria
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • leurocristine sulfate
  • Vincasar PFS
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS following treatment with rituximab intense dosing and CHOP-21 in previously untreated patients with high risk DLBCL
Time Frame: 1 year
Defined as the time from entry onto study until lymphoma progression or death from any cause.
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
CR in previously untreated patients with high risk DLBCL treated with rituximab intense dosing and CHOP-21
Time Frame: Baseline, between days 15 and 21 of course 3, and within 20-35 days after completion of treatment
Baseline, between days 15 and 21 of course 3, and within 20-35 days after completion of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fox Chase Cancer Center

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Michael Millenson, MD, FACP, Fox Chase Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

February 15, 2012

First Submitted That Met QC Criteria

February 21, 2012

First Posted (Estimate)

February 27, 2012

Study Record Updates

Last Update Posted (Estimate)

March 3, 2016

Last Update Submitted That Met QC Criteria

March 1, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OER-HM-039
  • NCI-2011-03309 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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