Home
Clinical Trials
Study Comparing Zevalin Regim...

Study Comparing Zevalin Regimen With no Further Treatment in Patients With Diffuse Large B-cell Lymphoma.

Last Updated: 2022-01-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-05-31

Study Completion Date

2008-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study treats patients with diffuse large B-cell lymphoma whose disease is in complete remission due to previous treatment with Cyclophosphamide Doxorubicin hydrochloride Vincristine Prednisolone- Rituximab (CHOP-R). Half of the patients received Zevalin and the other half receive no further anti-cancer treatment. The two patient groups compared to determine if Zevalin given after CHOP-R therapy provides greater benefits than receiving no additional anti-cancer therapy after CHOP-R.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Study of Zevalin Versus Observation in Participants at Least 60 Years Old With Newly Diagnosed Diffuse Large B-cell Lymphoma in Positron Emission Tomography (PET)-Negative Complete Remission After Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) or R-CHOP-like Therapy

NCT01510184

Diffuse Large B-cell Lymphoma Follicle Center Lymphoma

TERMINATED PHASE3

Yt90 Zevalin and Combination Chemotherapy (Z-CHOP)in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-cell Lymphoma

NCT00386321

Diffuse Large B-cell Lymphoma

TERMINATED PHASE2

Zevalin Twice in Aggressive Non-Hodgkin Lymphoma

NCT00902525

Diffuse Large B-Cell Lymphoma

TERMINATED PHASE2

Phase 3 Study of Zevalin Following R-CVP in Previously Untreated Patients With Follicular Non Hodgkin's Lymphoma (NHL)

NCT00384111

Follicular Lymphoma Lymphoma, Follicular

TERMINATED PHASE3

Study for Evaluation of Efficacy and Safety of SH L 749 to Indolent B-cell Non-Hodgkin's Lymphoma

NCT00220285

Non-Hodgkin's Lymphoma Lymphoma, B-Cell Lymphoma, Low-Grade

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The objectives of this study were to evaluate the efficacy and safety of the Zevalin study regimen compared with observation alone in patients with complete remission (CR or CRu) after first-line CHOP-R, the study was to include patients 60-years-of-age or older with histologically confirmed Ann Arbor stage II, III, or IV diffuse large B-cell lymphoma

End Points:

Primary endpoint: Overall survival (OS) Secondary endpoints: Disease-free survival (DFS), health-related quality of life (HRQL) as assessed by the patient using standard questionnaires .

Number of Patients :

A total of 400 patients (200 per arm) were planned to be enrolled.

\- In fact, 68 randomized patients (full analysis set; FAS) were analysed; 34 patients per each arm. The per-protocol set (PPS; 65 patients) comprised 33 patients allocated to the Zevalin arm and 32 patients allocated to the observation control arm.

Study Treatment :

The combination regimen with rituximab was designed in 2 steps as follows:

* Day 1: Initial administration of 250 mg/m\^2 rituximab, followed immediately by administration of 185 megabecquerel (MBq) (5 millicurie \[mCi\]) of \[111In\]-ibritumomab tiuxetan (the latter one only in centers where biodistribution imaging or dosimetry was compulsory according to local law). In centers where biodistribution imaging or dosimetry had not been required, the first rituximab infusion was given alone.
* Day 7-9: Rituximab 250 mg/m\^2, followed immediately by \[90Y\]-ibritumomab tiuxetan 14.8 megabecquerel/kilograms (MBq/kg) (0.4 millicurie / kilogram \[mCi/kg\]) (maximum dose 1184 MBq) given as a slow intravenous (I.V.) push over 10 minutes. Two treatment days one week apart followed by a 12-week safety period.

Duration of Patient Participation:

Due to the sequential design, the total duration of this study was not fixed. Originally, the study was planned in a randomized, parallel-group, group sequential design.

Objective :

The primary objective of this study was an inferential comparison between the 2 randomized groups in terms of overall survival using a group sequential triangular test ,since the study was prematurely terminated the pre-planned group-sequential nature of the study design was not applicable statistical analyses. Actually, the prominent efficacy variables for the OS and DFS were analysed in the FAS (identical to the safety analysis set) and PPS using Kaplan Meier estimates by treatment group.

Study Design :

This study was designed as a prospective, multi-center, open label, randomized, two-armed, group-sequential Phase III study. The study was planned to consist of 2 stages: an interventional Stage 1 with Screening/Baseline, treatment, safety, and follow-up periods, and a non-interventional Stage 2 consisting of a long-term follow-up period (until completion of a median observation period of 5 years). This second stage of the study was to be started only if superiority of the Zevalin study regimen could be demonstrated in the preceding Stage 1.

Pharmacokinetics/Pharmacodynamic results: Not applicable

Extent of exposure:

All 34 patients randomized to the Zevalin arm were given 2 rituximab infusions(with a median dose of 425.0 mg at each of the 2 infusion time points).Three patients underwent radioimaging studies/dosimetry and therefore were administered \[111In\]-ibritumomab tiuxetan at Day 1. All but 1 patient received an infusion with \[90Y\]-ibritumomab tiuxetan following the second infusion of rituximab. The mean dose ranged from 765.9 -1197.0 MBq.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Lymphoma, Large Cell, Diffuse

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Zevalin

Patients received Zevalin.

Zevalin Therapeutic Regimen:

Day 1: Initial administration of 250 mg/m\^2 rituximab, followed immediately by administration of 185 MBq of \[111In\]-ibritumomab tiuxetan ,in centers where centers where biodistribution imaging or dosimetry had not been required, the first rituximab infusion was given alone.

\- Day 7-9: Rituximab 250 mg/m\^2, followed immediately by \[90Y\]-ibritumomab tiuxetan 14.8 MBq/kg given as a slow intravenous push over 10 minutes.

Two treatment days one week apart were followed by a 12-week safety period.

Group Type EXPERIMENTAL

Zevalin

Intervention Type DRUG

Zevalin study treatment regimen consisted of 2 rituximab i.v. infusions (Day 1 and Day 7-9) and one \[90Y\]-ibritumomab tiuxetan infusion in connection with the second rituximab infusion.

The core treatment regimen in the Zevalin arm was:

Day 1: Rituximab i.v. infusion 250 mg/m\^2

Day 7-to 9: Rituximab i.v. infusion 250 mg/m\^2 immediately followed by \[90Y\]-ibritumomab tiuxetan 14.8 MBq/kg (0.4 mCi/kg) with a maximum dose of 1184 MBq (32 mCi),administered as slow intravenous push over 10 minutes.

Observational

Patients in this arm did not receive any reference therapy; they remained free of any anti-lymphoma therapy and were observed for relapse. This was non-interventional Stage consisting of a longterm follow-up period (until completion of a median observation period of 5 years).

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Zevalin

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Ibritumomab tiuxetan

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Histologically confirmed, Ann Arbor stage II, III, or IV Diffuse large B-cell lymphoma (DLBCL) according to the Revised European American Lymphoma(REAL)/World Health Organization (WHO) classification .
* Central pathology review confirming the DLBCL diagnosis and Cluster of differentiation 20 (CD20) positivity, and no evidence of DLBCL in bone marrow
* First-line treatment of DLBCL must have been 6 or 8 cycles of standard CHOP chemotherapy in combination with rituximab .
* Complete remission(CR) or unconfirmed complete remission(CRu) according to the International Workshop Response Criteria for Non Hodgkins Lymphoma (NHL) described by Cheson et al and modified for this study after first-line treatment with CHOP-R. Computerised Tomography (CT) scans of chest, abdomen, pelvis, and neck (if applicable) must have been performed within 6 weeks after the last dose of the last course of CHOP-R. Applicability of the neck CT means that the patient had involvement of the neck region by palpation / physical examination at first diagnosis (pre-CHOP-R).
* Central radiographic review of the CT scans from before and after first-line treatment with CHOP-R fulfilling the radiological requirements for CR/CRu
* Patients 60 years of age or older at time of randomization
* WHO performance status (PS) of 0 to 2 within 1 week of randomization
* Absolute neutrophil count greater than or equal to 1.5 x 10\^9/L within 1 week of randomization
* Hemoglobin greater than or equal to 10 g/dL within 1 week of randomization
* Platelets greater than or equal to 150 x 10\^9/L within 1 week of randomization
* Life expectancy of 3 months or longer
* Written informed consent obtained according to local guidelines

Exclusion Criteria

* Presence of any other malignancy or history of prior malignancy except non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma
* Prior radioimmunotherapy, radiation therapy, or any other NHL therapy except first-line CHOP-R
* Presence of gastric, central nervous system or testicular lymphoma at first diagnosis
* Histological transformation of low-grade non-Hodgkin's lymphoma (NHL)
* Known seropositivity for hepatitis C virus or hepatitis B surface antigen
* Known history of Human Immunodeficiency virus (HIV) infection
* Abnormal liver function: total bilirubin \> 1.5 x upper limit of normal (ULN) or Alanine Aminotransferase \> 2.5 x ULN within 1 week of randomization
* Abnormal renal function: serum creatinine \> 2.0 x ULN within 1 week of randomization
* Nonrecovery from the toxic effects of CHOP-R therapy
* Known hypersensitivity to murine or chimeric antibodies or proteins
* Granulocyte Colony Stimulating Factor (G-CSF) or Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) therapy within two weeks (or four weeks if pegylated) prior to screening laboratory sampling
* Concurrent severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes,congestive heart failure, myocardial infarction within 6 months of study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study
* Male and female patients of child-bearing potential unwilling to practice effective contraception during the study and unwilling or unable to continue contraception for 12 months after their last dose of study treatment
* Female patients who are pregnant or are currently breastfeeding
* Treatment with investigational drugs less than 4 weeks before the planned Day 1 or nonrecovery from the toxic effects of such therapy
* Surgery less than 4 weeks before the planned Day 1 or nonrecovery from the side effects of such surgery
* Concurrent systemic corticosteroid use for any reason except as premedication in case of known or suspected allergies to contrast media or as premedication for potential side effects of rituximab treatment
* Unwillingness or inability to comply with the protocol

Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers