Clinical trial NCT01510184: 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
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diffuse Large B-cell Lymphoma
Follicle Center Lymphoma
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2012-01-13
Enrollment: 79
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of Zevalin compared with observation alone in participants who are in PET-negative complete remission after first-line R-CHOP or R-CHOP like therapy.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Overall Survival (OS) for Living Participants
timeFrame: From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years)
measure: Overall Survival for Death
timeFrame: From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years)
measure: Overall Survival Rate at 24 Months
timeFrame: 24 Months
Other outcomes:
Locations:
city: Casa Grande
country: United States
facility: Cancer Treatment Services Arizona
state: Arizona
city: Berkeley
country: United States
facility: Sutter East Bay Hospitals
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Daytona Beach
country: United States
facility: Halifax Health Medical Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital Cancer Center
state: Georgia
city: Boise
country: United States
facility: St. Luke's Mountain States Tumor Institute (MSTI)
state: Idaho
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Specialists of Central Illinois
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Zion
country: United States
facility: Midwestern Regional Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute, Suburban
state: Kentucky
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Grosse Pointe Woods
country: United States
facility: St. John Hospital and Medical Center
state: Michigan
city: Saint Louis Park
country: United States
facility: Oncology Research-Park Nicollet Institute
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Hackensack
country: United States
facility: Hackensack UMC / John Theurer Cancer Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Gettysburg
country: United States
facility: Adams Cancer center
state: Pennsylvania
city: York
country: United States
facility: York Cancer Center / Cancer Care Associates of York
state: Pennsylvania
city: Greenville
country: United States
facility: Saint Francis Hospital
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Hematology and Transplant
state: South Dakota
city: Chattanooga
country: United States
facility: Associates In Oncology and Hematology
state: Tennessee
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Parkville
country: Australia
facility: Royal Melbourne
state: Victoria
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Geelong
country: Australia
facility: Barwon Health
city: Melbourne
country: Australia
facility: Western Hospital
city: Vienna
country: Austria
facility: Medizinische Universität Wien -AKH Wien
city: Bruxelles
country: Belgium
facility: Nuclear Medicine Physician, Jules Bordet Institute
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Sciences Centre-Regional Cancer Care
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Greenfield Park
country: Canada
facility: CSSS Champlain Charles LeMoyne
state: Quebec
city: Grenoble
country: France
facility: CHU A Michallon
state: Cedex 9
city: Limoges
country: France
facility: CHU Dupuytren
state: Cedex
city: Amiens
country: France
facility: CHU Amiens, Hôpital Sud
city: Avignon
country: France
facility: CH Avignon
city: Bayonne
country: France
facility: CH de la Côte Basque, Service d'Hématologie
city: Besancon
country: France
facility: Hématologie - CHU Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonié
city: Brest
country: France
facility: Hopital MORVAN - CHU Brest
city: Caen
country: France
facility: Centre François Baclesse, Comite Hématologie
city: Creteil
country: France
facility: Hôpital Henri MONDOR
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Lille
country: France
facility: CHRU Lille- Hospital Claude Huriez
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Metz
country: France
facility: CHR Metz-Thionville
city: Mulhouse
country: France
facility: CH de Mulhouse - Hôpital Emile Muller
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orleans
country: France
facility: CHR Orléans
city: Paris
country: France
facility: Institut Curie
city: Perpignan
country: France
facility: Centre Hospitalier Saint Jean
city: Pessac
country: France
facility: Hôpital Haut-Levêque Centre F.Magendie
city: Pontoise
country: France
facility: Centre Hospitalier René Dubos,
city: Rouen
country: France
facility: Service d'Hématologie Centre Henri Becquerel
city: Vandoeuvre-les-nancy
country: France
facility: CHU de Brabios
city: Dublin
country: Ireland
facility: St James 's Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Beersheba
country: Israel
facility: Soroka Medical Centre
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Centre
city: Tel-Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Bologna
country: Italy
facility: Policlinico S Orsola Malpighi, Istituto di Ematologia ''L.e A. Seragnoli''
city: Brescia
country: Italy
facility: New Ematologia dell'Ospedale "Spedali Civili" di Brescia
city: Milano
country: Italy
facility: Divisione di Ematoncologia
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea
city: Torino
country: Italy
facility: Azienda Ospedaliera San. Giovanni Battista di Torino, Dipartimento di Oncologia U.O.A Ematologia, Le Molinette,
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Den Haag
country: Netherlands
facility: Haga Ziekenhuis
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen (UMCG)
city: Hoofddorp
country: Netherlands
facility: Spaarne Ziekenhuis, Internal Medicine/Ocology
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
city: Nijmegen
country: Netherlands
facility: University Medical Center Radboud Nijmegen
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: San Juan
country: Puerto Rico
facility: Auxilio Mutuo Cancer Center
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra (CUN)
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Zaragoza
country: Spain
facility: Miguel Servet University Hospital
city: Bristol
country: United Kingdom
facility: Department of Haematology Bristol Royal Infirmary
city: Dorset
country: United Kingdom
facility: Poole General Hospital
city: Glasgow
country: United Kingdom
facility: Beatson Cancer Centre
city: London
country: United Kingdom
facility: King's College Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust, The Christie Hospital,
Study officials:
References: