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

NCT00322218 | Terminated Phase 3 Results DMC

• 1 other identifier: 307940/106-20
• Study Type: interventional
• Target: 68
• Locations: 19 countries
• Sites: 90

Brief Summary

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.

Conditions

Lymphoma, Large Cell, Diffuse

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  The primary analysis was based on the full analysis set (FAS). Actually, the prominent efficacy variable OS was analysed in the FAS (identical to the safety analysis set) and Per Protocol Set using Kaplan Meier estimates by treatment group. "Overall survival" was defined as the median time interval (in months)from randomization to death from any cause.This time-to-event variable was censored at the date of the last known follow-up visit (provided that the patient was still alive at that time).

  5 years or until patient dies or lost to follow up

Secondary Outcomes (2)

• Proportion of Participants With Disease Free Survival (DFS)

  5 years or until patient disease progresses or lost to follow up

• The Health-related Quality of Life (HRQL)

  Up to Month 36

Study Arms (2)

Zevalin

EXPERIMENTAL

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.

Drug: Zevalin

Observational

NO INTERVENTION

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).

Interventions

Zevalin 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.

Also known as: Ibritumomab tiuxetan

Zevalin

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Spectrum Pharmaceuticals, Inc: lead
• Bayer: collaborator

Study Sites (90)

Research Site

Mesa, Arizona, United States

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Phoenix, Arizona, United States

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Scottsdale, Arizona, United States

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Bakersfield, California, United States

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Berkeley, California, United States

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Beverly Hills, California, United States

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Burbank, California, United States

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Duarte, California, United States

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Los Angeles, California, United States

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Newport Beach, California, United States

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San Diego, California, United States

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Vallejo, California, United States

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Aurora, Colorado, United States

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Newark, Delaware, United States

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St. Petersburg, Florida, United States

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Coeur d'Alene, Idaho, United States

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Chicago, Illinois, United States

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Joliet, Illinois, United States

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Morris, Illinois, United States

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Overland Park, Kansas, United States

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Shreveport, Louisiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Rochester, Minnesota, United States

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Saint Louis Park, Minnesota, United States

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Commack, New York, United States

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East Setauket, New York, United States

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Durham, North Carolina, United States

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Philadelphia, Pennsylvania, United States

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Aberdeen, South Dakota, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Norfolk, Virginia, United States

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Graz, Austria

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Innsbruck, Austria

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Bruges, Belgium

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Ghent, Belgium

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Leuven, Belgium

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Edmonton, Alberta, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Helsinki, Finland

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Oulu, Finland

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Créteil, France

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Dijon, France

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Lille, France

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Limoges, France

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Lyon, France

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Paris, France

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Toulouse, France

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Chemnitz, Germany

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Jena, Germany

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Karlsruhe, Germany

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Mainz, Germany

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Rostock, Germany

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Würzburg, Germany

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Budapest, Hungary

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Debrecen, Hungary

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Szeged, Hungary

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Dublin, Ireland

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Galway, Ireland

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Bologna, Italy

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Milan, Italy

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Perugia, Italy

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Pisa, Italy

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Torino, Italy

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Gdansk, Poland

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Krakow, Poland

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Poznan, Poland

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Warsaw, Poland

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Coimbra, Portugal

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Lisbon, Portugal

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Porto, Portugal

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Singapore, Singapore

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Research Site, Yonsei

Seoul, South Korea

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Seoul, South Korea

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Madrid, Spain

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Pamplona, Spain

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Salamanca, Spain

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Seville, Spain

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Malmo, Sweden

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Uddevalla, Sweden

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Umeå, Sweden

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Bern, Switzerland

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Sankt Gallen, Switzerland

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Bangkok, Thailand

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Leicester, United Kingdom

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London, United Kingdom

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MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

The study was prematurely terminated after 68 patients had been randomized due to a low recruitment rate that would have led to an unacceptably long study duration.No safety concerns or lack of efficacy had led to the decision to cancel the study.

Results Point of Contact

• Title: Gajanan Bhat
• Organization: Spectrum Pharmaceuticals,Inc.

gajanan.bhat@sppirx.com

949-743-9219

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2006
• First Posted: May 5, 2006
• Study Start: May 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: January 19, 2022
• Results First Posted: January 19, 2022

Record last verified: 2022-01

Locations

DE (6); AU (2); KR (2); GB (2); FR (7); PL (4); ES (4); SG (1); FI (2); PT (3); HU (3); IT (5); CA (4); US (34); IE (2); SE (3); TH (1); CH (2); BE (3)