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 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: SPI-ZEV-11-301
• Study Type: interventional
• Target: 79
• Locations: 12 countries
• Sites: 92

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.

Conditions

Diffuse Large B-cell Lymphoma; Follicle Center Lymphoma

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS) for Living Participants

  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.

  From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years)

• Overall Survival for Death

  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.

  From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years)

Secondary Outcomes (2)

• Progression-Free Survival (PFS)

  From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years)

• Overall Survival Rate at 24 Months

  24 Months

Study Arms (2)

Zevalin

EXPERIMENTAL

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).

Drug: Zevalin; Drug: Y-90-Zevalin; Drug: Rituximab; Drug: In-111 Zevalin

Observation

NO INTERVENTION

Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease.

Interventions

Zevalin DRUG

Zevalin administered intravenous infusion.

Also known as: Ibritumomab Tiuxetan

Zevalin

Y-90-Zevalin DRUG

Y-90-Zevalin administered by intravenous infusion.

Zevalin

Rituximab DRUG

Rituximab administered by intravenous infusion.

Zevalin

In-111 Zevalin DRUG

In-111-Zevalin administered by intravenously.

Zevalin

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Spectrum Pharmaceuticals, Inc: lead

Study Sites (93)

Cancer Treatment Services Arizona

Casa Grande, Arizona, 85122, United States

Location

Sutter East Bay Hospitals

Berkeley, California, 94704, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Halifax Health Medical Center

Daytona Beach, Florida, 32114, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Piedmont Hospital Cancer Center

Atlanta, Georgia, 30318, United States

Location

St. Luke's Mountain States Tumor Institute (MSTI)

Boise, Idaho, 83712, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Decatur Memorial Hospital Cancer Care Specialists of Central Illinois

Decatur, Illinois, 62526, United States

Location

Illinois Cancer Specialists

Niles, Illinois, 60714, United States

Location

Midwestern Regional Medical Center

Zion, Illinois, 60099, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Norton Cancer Institute, Suburban

Louisville, Kentucky, 40207, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, 48236, United States

Location

Oncology Research-Park Nicollet Institute

Saint Louis Park, Minnesota, 55426, United States

Location

Saint Louis University

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89044, United States

Location

Hackensack UMC / John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Adams Cancer center

Gettysburg, Pennsylvania, 17325, United States

Location

York Cancer Center / Cancer Care Associates of York

York, Pennsylvania, 17403, United States

Location

Saint Francis Hospital

Greenville, South Carolina, 29601, United States

Location

Avera Hematology and Transplant

Sioux Falls, South Dakota, 57105, United States

Location

Associates In Oncology and Hematology

Chattanooga, Tennessee, 37421, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Royal Hobart Hospital

Hobart, Tasmania, 7001, Australia

Location

Royal Melbourne

Parkville, Victoria, 3052, Australia

Location

Royal Adelaide Hospital

Adelaide, Australia

Location

Barwon Health

Geelong, 3220, Australia

Location

Western Hospital

Melbourne, Australia

Location

Medizinische Universität Wien -AKH Wien

Vienna, A-1090, Austria

Location

Nuclear Medicine Physician, Jules Bordet Institute

Brussels, 1000, Belgium

Location

University Hospital Gasthuisberg

Leuven, 3000, Belgium

Location

Thunder Bay Regional Health Sciences Centre-Regional Cancer Care

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Sunnybrook Research Institute

Toronto, Ontario, Canada

Location

CSSS Champlain Charles LeMoyne

Greenfield Park, Quebec, J4V2H1, Canada

Location

CHU A Michallon

Grenoble, Cedex 9, 38043, France

Location

CHU Dupuytren

Limoges, Cedex, 87042, France

Location

CHU Amiens, Hôpital Sud

Amiens, 80054, France

Location

CH Avignon

Avignon, 84902, France

Location

CH de la Côte Basque, Service d'Hématologie

Bayonne, 64109, France

Location

Hématologie - CHU Jean Minjoz

Besançon, 25030, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Hopital MORVAN - CHU Brest

Brest, 29609, France

Location

Centre François Baclesse, Comite Hématologie

Caen, 14076, France

Location

Hôpital Henri MONDOR

Créteil, 94010, France

Location

CHD Vendée

La Roche-sur-Yon, 85925, France

Location

CHRU Lille- Hospital Claude Huriez

Lille, 59037, France

Location

Institut Paoli-Calmettes

Marseille, 13273, France

Location

CHR Metz-Thionville

Metz, 57085, France

Location

CH de Mulhouse - Hôpital Emile Muller

Mulhouse, 68100, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

CHR Orléans

Orléans, 45100, France

Location

Institut Curie

Paris, 75005, France

Location

Centre Hospitalier Saint Jean

Perpignan, 66000, France

Location

Hôpital Haut-Levêque Centre F.Magendie

Pessac, 33600, France

Location

Centre Hospitalier René Dubos,

Pontoise, 95303, France

Location

Service d'Hématologie Centre Henri Becquerel

Rouen, 76038, France

Location

CHU de Brabios

Vandœuvre-lès-Nancy, 54511, France

Location

St James 's Hospital

Dublin, 8, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

Soroka Medical Centre

Beersheba, 84101, Israel

Location

Rambam Health Care Campus

Haifa, Israel

Location

Hadassah Medical Organization

Jerusalem, 91120, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 93722, Israel

Location

Tel Aviv Sourasky Medical Centre

Tel Aviv, 64239, Israel

Location

Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Policlinico S Orsola Malpighi, Istituto di Ematologia ''L.e A. Seragnoli''

Bologna, 40138, Italy

Location

New Ematologia dell'Ospedale "Spedali Civili" di Brescia

Brescia, 25123, Italy

Location

Divisione di Ematoncologia

Milan, 20141, Italy

Location

Azienda Ospedaliera Sant'Andrea

Roma, 00189, Italy

Location

Azienda Ospedaliera San. Giovanni Battista di Torino, Dipartimento di Oncologia U.O.A Ematologia, Le Molinette,

Torino, 10126, Italy

Location

Meander Medisch Centrum

Amersfoort, 3813 TZ, Netherlands

Location

VU Medisch Centrum

Amsterdam, 1081, Netherlands

Location

University Medical Centre Groningen (UMCG)

Groningen, 9713GZ, Netherlands

Location

Spaarne Ziekenhuis, Internal Medicine/Ocology

Hoofddorp, 2134TM, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, 8934 AD, Netherlands

Location

St. Antonius Hospital

Nieuwegein, 3435 CM, Netherlands

Location

University Medical Center Radboud Nijmegen

Nijmegen, 6525, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, NL-3015, Netherlands

Location

Haga Ziekenhuis

The Hague, 2545 CH, Netherlands

Location

Auxilio Mutuo Cancer Center

San Juan, 00918, Puerto Rico

Location

Clínica Universidad de Navarra (CUN)

Pamplona, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Miguel Servet University Hospital

Zaragoza, Spain

Location

Department of Haematology Bristol Royal Infirmary

Bristol, BS2 8HW, United Kingdom

Location

Poole General Hospital

Dorset, BH15, United Kingdom

Location

Beatson Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

The Christie NHS Foundation Trust, The Christie Hospital,

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Interventions

ibritumomab tiuxetan; Rituximab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated early due to a sponsor business decision.

Results Point of Contact

• Title: Gajanan Bhat, PhD
• Organization: Spectrum Pharmaceuticals

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: January 6, 2012
• First Posted: January 13, 2012
• Study Start: April 19, 2012
• Primary Completion: October 23, 2014
• Study Completion: October 23, 2014
• Last Updated: December 16, 2021
• Results First Posted: December 16, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); IE (2); IT (5); IL (6); NL (9); ES (3); CA (3); FR (23); US (28); PR (1); GB (5); BE (2)