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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2014 by Fox Chase Cancer Center
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Fox Chase Cancer Center
ClinicalTrials.gov Identifier:
NCT01539174
First received: February 15, 2012
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
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
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Drug: prednisone
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Fox Chase Cancer Center:

Primary Outcome Measures:
  • PFS following treatment with rituximab intense dosing and CHOP-21 in previously untreated patients with high risk DLBCL [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, between days 15 and 21 of course 3, and within 20-35 days after completion of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 61
Study Start Date: July 2014
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01539174

Locations
United States, Pennsylvania
Fox Chase Cancer Center Not yet recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Michael Millenson, MD. FACP    215-728-6900    michael.millenson@fccc.edu   
Principal Investigator: Michael Millenson, MD, FACP         
Sponsors and Collaborators
Fox Chase Cancer Center
Genentech, Inc.
Investigators
Principal Investigator: Michael Millenson, MD, FACP Fox Chase Cancer Center
  More Information

No publications provided

Responsible Party: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT01539174     History of Changes
Other Study ID Numbers: OER-HM-039, NCI-2011-03309
Study First Received: February 15, 2012
Last Updated: March 17, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies, Monoclonal
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Prednisone
Rituximab
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on October 23, 2014