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

Primary Purpose

Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage I Adult Diffuse Large Cell Lymphoma

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rituximab
cyclophosphamide
doxorubicin hydrochloride
vincristine sulfate
prednisone
laboratory biomarker analysis
pharmacological study
Sponsored by
Fox Chase Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Contiguous Stage II Adult Diffuse Large Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fox Chase Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (monoclonal antibody, combination chemotherapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

CR in previously untreated patients with high risk DLBCL treated with rituximab intense dosing and CHOP-21

Full Information

First Posted
February 15, 2012
Last Updated
March 1, 2016
Sponsor
Fox Chase Cancer Center
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01539174
Brief Title
Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated High- or High-Intermediate-Risk Diffuse Large B-Cell Lymphoma
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Withdrawn
Why Stopped
No Funding Source and Competing Trials
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fox Chase Cancer Center
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (monoclonal antibody, combination chemotherapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Other Intervention Name(s)
ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Other Intervention Name(s)
leurocristine sulfate, VCR, Vincasar PFS
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
prednisone
Other Intervention Name(s)
DeCortin, Deltra
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
PFS following treatment with rituximab intense dosing and CHOP-21 in previously untreated patients with high risk DLBCL
Description
Defined as the time from entry onto study until lymphoma progression or death from any cause.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Millenson, MD, FACP
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111-2497
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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