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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01510184




Registration number
NCT01510184
Ethics application status
Date submitted
6/01/2012
Date registered
13/01/2012

Titles & IDs
Public title
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
Scientific title
A Phase 3, Open-label, Multicenter, Randomized Study of Sequential Zevalin (Ibritumomab Tiuxetan) Versus Observation in Patients at Least 60 Years of Age With Newly Diagnosed Diffuse Large B-cell Lymphoma in PET-negative Complete Remission After R-CHOP or R-CHOP-like Therapy
Secondary ID [1] 0 0
SPI-ZEV-11-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B-cell Lymphoma 0 0
Follicle Center Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Zevalin
Treatment: Drugs - Y-90-Zevalin
Treatment: Drugs - Rituximab
Treatment: Drugs - In-111 Zevalin

Experimental: Zevalin - Participants received rituximab 250 milligram per meter square (mg/m\^2) by intravenous infusion on Day 1. If required by the governing regulatory agency, rituximab was to be followed 4 hours later by In-111-Zevalin 5.0 millicurie (mCi) on Day 1. And on Days 7-9: participants received rituximab 250 mg/m\^2 by intravenous infusion, followed 4 hours later by Y-90-Zevalin 0.4 millicurie/kilogram (mCi/kg) 10-minute intravenous push (0.3 mCi/kg in participants with a platelet count in 100,000/ microliter \[µL\] to 149,000/µL).

No intervention: Observation - Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease.


Treatment: Drugs: Zevalin
Zevalin administered intravenous infusion.

Treatment: Drugs: Y-90-Zevalin
Y-90-Zevalin administered by intravenous infusion.

Treatment: Drugs: Rituximab
Rituximab administered by intravenous infusion.

Treatment: Drugs: In-111 Zevalin
In-111-Zevalin administered by intravenously.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) for Living Participants
Timepoint [1] 0 0
From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years)
Primary outcome [2] 0 0
Overall Survival for Death
Timepoint [2] 0 0
From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years)
Secondary outcome [1] 0 0
Progression-Free Survival (PFS)
Timepoint [1] 0 0
From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years)
Secondary outcome [2] 0 0
Overall Survival Rate at 24 Months
Timepoint [2] 0 0
24 Months

Eligibility
Key inclusion criteria
1. Participant was 60-years of age or older at time of randomization
2. Histologically confirmed Ann Arbor stage II, III, or IV diffuse large B-cell lymphoma (DLBCL); or follicular lymphoma (FCL) Grade 3B according to the Revised European American lymphoma (REAL)/ World health organization (WHO) classification (from initial diagnosis made prior to starting R-CHOP therapy. Results from a pre R-CHOP marrow shall be available for review.
3. Local pathology review confirming the DLBCL diagnosis and cluster of differentiation 20 (CD20) positivity, and no evidence of DLBCL in bone marrow upon confirmation of complete remission (CR).
4. A paraffin block or original slides available for confirmatory pathology review. Participants may be randomized based on the local pathology result.
5. Age-adjusted international prognostic index (IPI) of 1, 2, or 3. The age-adjusted IPI was defined by one point for Lactate dehydrogenase (LDH) > upper limit of normal (ULN); Stage III or IV; and Karnofsky performance status <80% or WHO/ eastern cooperative operations group (ECOG) performance status >1.
6. First-line treatment of DLBCL must have been 6 cycles of standard R-CHOP21, R-CHOP14 or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) chemotherapy. Participants who received pre-phase therapy for the purpose of improving performance status prior to initiating R-CHOP are eligible.
7. Complete remission (CR) according to the International Workshop Response Criteria for non-Hodgkin's lymphoma (NHL) described by Cheson et al after first-line treatment. Computerized 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 chemotherapy. Applicability of the neck CT means that the participant had involvement of the neck region by palpation / physical examination at first diagnosis.
8. A negative Fluorine-18-deoxyglucose positron emission tomography (FDG-PET) scan confirming complete response, with negative defined as a score of 1-3 on the Deauville 5-point scale used to quantify radionucleotide density in PET scans as determined locally (Morschhauser 200735).
9. Bone marrow cellularity greater than 15%, no evidence of myelodysplasia morphologically and no evidence of involvement with lymphoma either at the pre R-CHOP marrow or on repeat assessment pre-Zevalin. After completing R-chemotherapy, a repeat marrow is required for participant randomized to the Zevalin arm only.
10. A world health organization/eastern cooperative oncology group (WHO/ECOG) performance status of 0, 1 or 2.
11. Adequate hematopoietic functions: Absolute neutrophil count (ANC) = 1.0 x 10^9/ liter (L), Hemoglobin (Hgb) = 9 g/dL, Platelets = 100 x 10^9/L.
12. Life expectancy of 6 months or longer.
13. Written informed consent obtained according to local guidelines.
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of any other malignancy or history of prior malignancy within 5 years of study entry. Within 5 years, participants treated for Stage I or II cancers are eligible provided they have a life expectancy of > 5 years. The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ cervical cancer.
2. Prior radioimmunotherapy, including radiation therapy for Non-Hodgkin's lymphoma) NHL, or any other NHL therapy.
3. Presence of primary gastric, central nervous system (CNS), or testicular lymphoma at first diagnosis.
4. Histological transformation of low-grade NHL.
5. Active hepatitis B or C.
6. Known history of human immunodeficiency virus (HIV) infection.
7. Abnormal liver function: total bilirubin > 2 × ULN unless secondary to Gilbert disease.
8. Abnormal renal function: serum creatinine > 2.0 × ULN.
9. Non-recovery from the toxic effects of chemotherapy to < grade 2, or interfering with Zevalin treatment.
10. Known hypersensitivity to murine or chimeric antibodies or proteins.
11. Granulocyte-colony stimulating factor (G-CSF) or Granulocyte macrophage-colony stimulating factor (GM-CSF) therapy within 4 weeks prior to Zevalin or observation.
12. Concurrent severe and/or medically uncontrolled 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.
13. Treatment with investigational drugs less than 4 weeks prior to Zevalin or observation.
14. Major surgery less than 4 weeks prior to Zevalin or start of observation.
15. 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. Participants on a chronic dose of prednisone for a medical condition (e.g. Asthma or autoimmune disease) less than or equal to 20 milligram (mg) daily, stable for 4 weeks, are permissible.
16. Unwillingness or inability to comply with the protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/04/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/10/2014
Sample size
Target
Accrual to date
Final
79
Recruitment in Australia
Recruitment state(s)
TAS,VIC
Recruitment hospital [1] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [2] 0 0
Royal Melbourne - Parkville
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Barwon Health - Geelong
Recruitment hospital [5] 0 0
Western Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
7001 - Hobart
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
3220 - Geelong
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
California
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United States of America
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Florida
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United States of America
State/province [4] 0 0
Georgia
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Idaho
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United States of America
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Illinois
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United States of America
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Iowa
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United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
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Massachusetts
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United States of America
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Michigan
Country [11] 0 0
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Minnesota
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Missouri
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Nevada
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New Jersey
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New York
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Pennsylvania
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South Carolina
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South Dakota
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State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
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United States of America
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Washington
Country [22] 0 0
Austria
State/province [22] 0 0
Vienna
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Belgium
State/province [23] 0 0
Bruxelles
Country [24] 0 0
Belgium
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Leuven
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Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
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France
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Cedex 9
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France
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Cedex
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France
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Amiens
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France
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Avignon
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France
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Bayonne
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France
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Besancon
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France
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Bordeaux
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France
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Brest
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France
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Caen
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France
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Creteil
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France
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La Roche-sur-Yon
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France
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Lille
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France
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Marseille
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France
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Metz
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France
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Mulhouse
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France
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Nice
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France
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Orleans
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France
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Paris
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France
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Perpignan
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France
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Pessac
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France
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Pontoise
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France
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Rouen
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France
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Vandoeuvre-les-nancy
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Ireland
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Dublin
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Ireland
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Galway
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Israel
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Beersheba
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Tel Aviv
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Israel
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Tel-Hashomer
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Italy
State/province [57] 0 0
Bologna
Country [58] 0 0
Italy
State/province [58] 0 0
Brescia
Country [59] 0 0
Italy
State/province [59] 0 0
Milano
Country [60] 0 0
Italy
State/province [60] 0 0
Roma
Country [61] 0 0
Italy
State/province [61] 0 0
Torino
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Netherlands
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Amersfoort
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Netherlands
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Amsterdam
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Netherlands
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Den Haag
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Netherlands
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Groningen
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Netherlands
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Hoofddorp
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Netherlands
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Leeuwarden
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Netherlands
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Nieuwegein
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Netherlands
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Nijmegen
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Netherlands
State/province [70] 0 0
Rotterdam
Country [71] 0 0
Puerto Rico
State/province [71] 0 0
San Juan
Country [72] 0 0
Spain
State/province [72] 0 0
Pamplona
Country [73] 0 0
Spain
State/province [73] 0 0
Zaragoza
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Bristol
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Dorset
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United Kingdom
State/province [76] 0 0
Glasgow
Country [77] 0 0
United Kingdom
State/province [77] 0 0
London
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Spectrum Pharmaceuticals, Inc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01510184