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
- Conditions
- Diffuse Large B-cell LymphomaFollicle Center Lymphoma
- Interventions
- Registration Number
- NCT01510184
- Lead Sponsor
- Spectrum Pharmaceuticals, Inc
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 79
- Participant was 60-years of age or older at time of randomization
- 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.
- 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).
- A paraffin block or original slides available for confirmatory pathology review. Participants may be randomized based on the local pathology result.
- 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.
- 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.
- 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.
- 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).
- 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.
- A world health organization/eastern cooperative oncology group (WHO/ECOG) performance status of 0, 1 or 2.
- 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.
- Life expectancy of 6 months or longer.
- Written informed consent obtained according to local guidelines.
- 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.
- Prior radioimmunotherapy, including radiation therapy for Non-Hodgkin's lymphoma) NHL, or any other NHL therapy.
- Presence of primary gastric, central nervous system (CNS), or testicular lymphoma at first diagnosis.
- Histological transformation of low-grade NHL.
- Active hepatitis B or C.
- Known history of human immunodeficiency virus (HIV) infection.
- Abnormal liver function: total bilirubin > 2 × ULN unless secondary to Gilbert disease.
- Abnormal renal function: serum creatinine > 2.0 × ULN.
- Non-recovery from the toxic effects of chemotherapy to < grade 2, or interfering with Zevalin treatment.
- 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 4 weeks prior to Zevalin or observation.
- 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.
- Treatment with investigational drugs less than 4 weeks prior to Zevalin or observation.
- Major surgery less than 4 weeks prior to Zevalin or start of observation.
- 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.
- Unwillingness or inability to comply with the protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Zevalin In-111 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). Zevalin 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). Zevalin Y-90-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). Zevalin Rituximab 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).
- Primary Outcome Measures
Name Time Method Overall Survival (OS) for Living Participants From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years) OS was the time from randomization to death. In living participants, survival time was censored on the last date that participants were known to be alive. OS for living participant was calculated as (end of study date/last visit date - randomization date)+ 1/30.4375. Overall Survival was summarized separately for living participants as only few participants died in this study.
Overall Survival for Death From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years) OS was the time from randomization to death. OS for death calculated as (date of death - randomization date)+ 1/30.4375. Overall Survival was summarized separately for participants who were died as only few participants died in this study.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years) PFS was defined as the time interval between the date of randomization and the date of relapse or death from any cause.
Overall Survival Rate at 24 Months 24 Months The OS rate at 24-month defined as the percentage of all randomized participants who died within 24 months of randomization.
Trial Locations
- Locations (93)
Hackensack UMC / John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
CHU Dupuytren
🇫🇷Limoges, Cedex, France
Chaim Sheba Medical Center
🇮🇱Tel-Hashomer, Israel
Comprehensive Cancer Centers of Nevada
🇺🇸Henderson, Nevada, United States
Institut Paoli-Calmettes
🇫🇷Marseille, France
Centre Antoine Lacassagne
🇫🇷Nice, France
CHR Orléans
🇫🇷Orleans, France
CHD Vendée
🇫🇷La Roche-sur-Yon, France
Centre Hospitalier Saint Jean
🇫🇷Perpignan, France
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Norton Cancer Institute, Suburban
🇺🇸Louisville, Kentucky, United States
York Cancer Center / Cancer Care Associates of York
🇺🇸York, Pennsylvania, United States
Sutter East Bay Hospitals
🇺🇸Berkeley, California, United States
Cancer Treatment Services Arizona
🇺🇸Casa Grande, Arizona, United States
Decatur Memorial Hospital Cancer Care Specialists of Central Illinois
🇺🇸Decatur, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Avera Hematology and Transplant
🇺🇸Sioux Falls, South Dakota, United States
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Royal Melbourne
🇦🇺Parkville, Victoria, Australia
The University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Barwon Health
🇦🇺Geelong, Australia
University Hospital Gasthuisberg
🇧🇪Leuven, Belgium
Thunder Bay Regional Health Sciences Centre-Regional Cancer Care
🇨🇦Thunder Bay, Ontario, Canada
Nuclear Medicine Physician, Jules Bordet Institute
🇧🇪Bruxelles, Belgium
CH Avignon
🇫🇷Avignon, France
CH de la Côte Basque, Service d'Hématologie
🇫🇷Bayonne, France
Hôpital Henri MONDOR
🇫🇷Creteil, France
CHRU Lille- Hospital Claude Huriez
🇫🇷Lille, France
Hôpital Haut-Levêque Centre F.Magendie
🇫🇷Pessac, France
St James 's Hospital
🇮🇪Dublin, Ireland
Centre Hospitalier René Dubos,
🇫🇷Pontoise, France
Service d'Hématologie Centre Henri Becquerel
🇫🇷Rouen, France
University Hospital Galway
🇮🇪Galway, Ireland
Rambam Health Care Campus
🇮🇱Haifa, Israel
Soroka Medical Centre
🇮🇱Beersheba, Israel
Hadassah Medical Organization
🇮🇱Jerusalem, Israel
Tel Aviv Sourasky Medical Centre
🇮🇱Tel Aviv, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
New Ematologia dell'Ospedale "Spedali Civili" di Brescia
🇮🇹Brescia, Italy
Meander Medisch Centrum
🇳🇱Amersfoort, Netherlands
Azienda Ospedaliera San. Giovanni Battista di Torino, Dipartimento di Oncologia U.O.A Ematologia, Le Molinette,
🇮🇹Torino, Italy
Azienda Ospedaliera Sant'Andrea
🇮🇹Roma, Italy
VU Medisch Centrum
🇳🇱Amsterdam, Netherlands
Haga Ziekenhuis
🇳🇱Den Haag, Netherlands
University Medical Centre Groningen (UMCG)
🇳🇱Groningen, Netherlands
Spaarne Ziekenhuis, Internal Medicine/Ocology
🇳🇱Hoofddorp, Netherlands
Medisch Centrum Leeuwarden
🇳🇱Leeuwarden, Netherlands
St. Antonius Hospital
🇳🇱Nieuwegein, Netherlands
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Department of Haematology Bristol Royal Infirmary
🇬🇧Bristol, United Kingdom
Clínica Universidad de Navarra (CUN)
🇪🇸Pamplona, Spain
Miguel Servet University Hospital
🇪🇸Zaragoza, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Poole General Hospital
🇬🇧Dorset, United Kingdom
The Christie NHS Foundation Trust, The Christie Hospital,
🇬🇧Manchester, United Kingdom
Oncology Research-Park Nicollet Institute
🇺🇸Saint Louis Park, Minnesota, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
City of Hope
🇺🇸Duarte, California, United States
Halifax Health Medical Center
🇺🇸Daytona Beach, Florida, United States
St. Luke's Mountain States Tumor Institute (MSTI)
🇺🇸Boise, Idaho, United States
Illinois Cancer Specialists
🇺🇸Niles, Illinois, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States
Adams Cancer center
🇺🇸Gettysburg, Pennsylvania, United States
Piedmont Hospital Cancer Center
🇺🇸Atlanta, Georgia, United States
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Midwestern Regional Medical Center
🇺🇸Zion, Illinois, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Western Hospital
🇦🇺Melbourne, Australia
Associates In Oncology and Hematology
🇺🇸Chattanooga, Tennessee, United States
Medizinische Universität Wien -AKH Wien
🇦🇹Vienna, Austria
CHU A Michallon
🇫🇷Grenoble, Cedex 9, France
CHU Amiens, Hôpital Sud
🇫🇷Amiens, France
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
CSSS Champlain Charles LeMoyne
🇨🇦Greenfield Park, Quebec, Canada
Hématologie - CHU Jean Minjoz
🇫🇷Besancon, France
Hopital MORVAN - CHU Brest
🇫🇷Brest, France
Institut Bergonié
🇫🇷Bordeaux, France
Centre François Baclesse, Comite Hématologie
🇫🇷Caen, France
CHR Metz-Thionville
🇫🇷Metz, France
CH de Mulhouse - Hôpital Emile Muller
🇫🇷Mulhouse, France
Institut Curie
🇫🇷Paris, France
CHU de Brabios
🇫🇷Vandoeuvre-les-nancy, France
Policlinico S Orsola Malpighi, Istituto di Ematologia ''L.e A. Seragnoli''
🇮🇹Bologna, Italy
Divisione di Ematoncologia
🇮🇹Milano, Italy
University Medical Center Radboud Nijmegen
🇳🇱Nijmegen, Netherlands
Auxilio Mutuo Cancer Center
🇵🇷San Juan, Puerto Rico
Beatson Cancer Centre
🇬🇧Glasgow, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States