Suspended

A Phase II Trial of R-CHOP Followed by Zevalin Radioimmunotherapy for Patients With Previously Untreated Stages I and II CD20+ Diffuse Large Cell Non-Hodgkin's Lymphoma

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What is being tested

rituximab

+ prednisone
+ cyclophosphamide
Biological
Drug
Radiation
Procedure
Who is being recruted

Blood Protein Disorders
+17

+ Cardiovascular Diseases
+ Hematologic Diseases
Over 18 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 2
Interventional
Study Start: December 2004
See protocol details

Summary

Principal SponsorNational Cancer Institute (NCI)
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: December 1, 2004Actual date on which the first participant was enrolled.

PRIMARY OBJECTIVES: I. To evaluate the complete response rate (CR) and functional CR rate in patients with previously untreated stage I (with at least 1 risk factor) or stage II CD20+ diffuse large cell lymphoma who receive therapy with R-CHOP followed by 90-Yttrium -Zevalin™. SECONDARY OBJECTIVES: I. To evaluate the time to treatment failure, duration of response, and overall survival in these patients who receive therapy with R-CHOP followed by 90-Yttrium -Zevalin™. II. To evaluate the toxicity of this therapy. III. To evaluate the toxicity of adding involved field radiation therapy > 12 weeks after Zevalin™ for patients with CT+/PET+ residual masses. TERTIARY OBJECTIVES: I. To evaluate PET scans pre -and post - R-CHOP/Zevalin™ therapy. OUTLINE: R-CHOP (rituximab, prednisone, cyclophosphamide, doxorubicin,vincristine): Patients receive oral prednisone once daily on days 1-5. Patients also receive rituximab IV over several hours followed by cyclophosphamide IV, doxorubicin IV, and vincristine IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) after 2 courses receive 2 additional courses. Patients achieving a partial response, uncertain CR, or stable disease receive 4 additional courses. Patients are evaluated 3 weeks after the last course of therapy. Patients with progressive disease go off study. Radioimmunotherapy: Beginning no more than 9 weeks after the reevaluation (or 12 weeks after the last dose of R-CHOP), patients receive rituximab IV on day 1 followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes for imaging studies. Patients then receive rituximab IV followed by yttrium 90-Yttrium ibritumomab tiuxetan IV over 10 minutes on day 8. Radiotherapy: Patients with residual disease by CT scan or positron emission tomography (PET) scan after 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually for 5 years.

Official TitleA Phase II Trial of R-CHOP Followed by Zevalin Radioimmunotherapy for Patients With Previously Untreated Stages I and II CD20+ Diffuse Large Cell Non-Hodgkin's Lymphoma 
NCT00088881
Principal SponsorNational Cancer Institute (NCI)
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
62 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation
: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.

Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment
: Participants are split into separate groups, each receiving a different treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Waldenstrom Macroglobulinemia
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell, Marginal Zone
Hemostatic Disorders
Neoplasms, Plasma Cell
Criteria

Inclusion Criteria: * Patients must have histologically confirmed diagnosis of diffuse large cell lymphoma * Patients must be stage I or II (Modified Ann Arbor staging) * Baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by CT scan or other appropriate imaging; patients must have at least one objective measurable disease parameter (a lesion with at least 1 dimension \> 1.5 cm); or if they are stage 1 * Stage I patients must have at least one of the following risk factors: * Age \>= 60 years * Bulky disease (\>= 5 cm in at least one dimension) * Elevated Lactate Dehydrogenase (LDH) above institutional upper limit of normal * Eastern Cooperative Oncology Group (ECOG) performance status = 2 * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Absolute neutrophil count \>= 1500/mm\^3 (includes neutrophils and bands) * Platelet count \>= 100,000/mm\^3 * Creatinine \< 2.0 mg/dl * Total bilirubin \< 2 mg/dl (may be up to 3.0 mg/dl if due to liver involvement by lymphoma); patients with elevated total bilirubin should have a direct bilirubin checked; if the direct bilirubin is normal there is no need for a dose reduction * Patients must have left ventricular ejection fraction (LVEF) of \> 45% * Patients must be tested for hepatitis B (HBV) surface antigen within 2 weeks of registration * NOTE: Patients who test positive will be allowed to participate but must be followed closely for clinical and laboratory signs of active HBV infection and for signs of hepatitis Exclusion Criteria: * Prior chemotherapy, radiation therapy, radioimmunotherapy, or immunotherapy; a short course (=\< 14 days prior to registration) of corticosteroids is allowed * Evidence of other malignancy: * Prior chemotherapy or prior radiation therapy for other malignancies * Currently receiving hormone therapy or chemotherapy for another malignancy even if the treatment is being provided in the adjuvant treatment setting, i.e. with no evidence of the original other malignancy * Adjuvant hormonal therapy must have been discontinued \> 3 months before entering this study * Patients are eligible if they meet the following conditions: (a) treated carcinoma-in-situ of the cervix; (b) treated squamous cell or basal cell skin cancer; or (c) any other surgically cured malignancy from which the patient has been disease free for at least 3 years * Pregnant or breast feeding, as there would be radiation exposure to the fetus or child; a negative pregnancy test is required =\< 1 week prior to registration for women of childbearing potential (WOCBP). Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception * Known central nervous system (CNS) lymphoma, testicular lymphoma, or vitreous lymphoma * Known HIV infection. The safety of Zevalin™ in this population has not been tested at this time * Serious coexisting medical condition or active infection which would compromise the ability to deliver standard R-CHOP chemotherapy * Evidence of myelodysplasia on bone marrow aspiration and biopsy


Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
One single intervention group 

is designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone): Patients receive R-CHOP every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response after 2 courses receive 2 additional courses. Patients achieving a partial response, uncertain CR, or stable disease receive 4 additional courses. Patients with progressive disease go off study. Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, patients receive rituximab IV on day 1 followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes for imaging studies. Patients then receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8. Radiation therapy: Patients with residual disease by CT scan or positron emission tomography (PET) scan after 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy.

Given IV

Given orally

Given IV

Given IV

Given IV

Given IV

Undergo radiotherapy

Undergo PET scans
Study Objectives
Primary Objectives

Response was assessed based upon the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma (Cheson, 1999). CR is defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related B-symptoms if present prior to therapy, as well as normalization (normal limits of institutional labs) of those biochemical abnormalities (e.g., LDH) definitely attributed to NHL. CRu is defined as meeting the criteria of CR except one or more of the followings: A residual dominant node (or extra-nodal mass) that is currently \> 1.5 cm in greatest diameter that has decreased by \> 75% from baseline in the product of its diameters. Individual dominant nodes (or extra-nodal masses) that were previously confluent must have decreased by \> 75% in SPD compared with the size of the original mass. Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia).

Patients will be considered a functional CR if they meet the criteria for a CR, or if they meet the criteria for a CRu or partial response (PR) by CT and are PET negative. Please see primary outcome #1 for the definition of CR and CRu. PR is defined as: A decrease of \>50% in the SPD (sum of products of the diameters) of the six largest (or less) dominant nodes or extra-nodal masses. No increase in the size of the liver or the spleen. No unequivocal progression in any non-measurable or non-dominant site. Splenic and hepatic nodules must regress by \>50% in SPD (sum of the products of the diameters). Bone marrow assessment is not relevant for determination of a PR because it is assessable and not measurable disease. No new sites of disease.
Secondary Objectives

Time to treatment failure (TTF) is defined as the time from step 1 registration to disease progression or death. TTF is censored at last documented progression free for cases without progression. The 3-year TTF rate is defined as the probability of patients remaining free from treatment failure at 3 years.

Overall survival (OS) is defined as the time from step 1 registration to death of any cause. OS is censored at the date last known alive for cases that are alive. The 3-year OS rate is defined as the probability of patients remaining alive at 3 years.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 1 location
Suspended
Eastern Cooperative Oncology GroupBoston, United StatesSee the location

SuspendedOne Study Center
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