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

NCT ID: NCT01510184

Last Updated: 2021-12-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-19
• Study Completion Date: 2014-10-23

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Zevalin

Intervention Type: DRUG

Zevalin administered intravenous infusion.

Y-90-Zevalin

Intervention Type: DRUG

Y-90-Zevalin administered by intravenous infusion.

Rituximab

Intervention Type: DRUG

Rituximab administered by intravenous infusion.

In-111 Zevalin

Intervention Type: DRUG

In-111-Zevalin administered by intravenously.

Observation

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Zevalin

Zevalin administered intravenous infusion.

Intervention Type: DRUG

Y-90-Zevalin

Y-90-Zevalin administered by intravenous infusion.

Intervention Type: DRUG

Rituximab

Rituximab administered by intravenous infusion.

Intervention Type: DRUG

In-111 Zevalin

In-111-Zevalin administered by intravenously.

Intervention Type: DRUG

Other Intervention Names

Ibritumomab Tiuxetan

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.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spectrum Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cancer Treatment Services Arizona

Casa Grande, Arizona, United States

Sutter East Bay Hospitals

Berkeley, California, United States

City of Hope

Duarte, California, United States

Halifax Health Medical Center

Daytona Beach, Florida, United States

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Piedmont Hospital Cancer Center

Atlanta, Georgia, United States

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

Boise, Idaho, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Decatur Memorial Hospital Cancer Care Specialists of Central Illinois

Decatur, Illinois, United States

Illinois Cancer Specialists

Niles, Illinois, United States

Midwestern Regional Medical Center

Zion, Illinois, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Norton Cancer Institute, Suburban

Louisville, Kentucky, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Oncology Research-Park Nicollet Institute

Saint Louis Park, Minnesota, United States

Saint Louis University

St Louis, Missouri, United States

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Hackensack UMC / John Theurer Cancer Center

Hackensack, New Jersey, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Adams Cancer center

Gettysburg, Pennsylvania, United States

York Cancer Center / Cancer Care Associates of York

York, Pennsylvania, United States

Saint Francis Hospital

Greenville, South Carolina, United States

Avera Hematology and Transplant

Sioux Falls, South Dakota, United States

Associates In Oncology and Hematology

Chattanooga, Tennessee, United States

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Royal Hobart Hospital

Hobart, Tasmania, Australia

Royal Melbourne

Parkville, Victoria, Australia

Royal Adelaide Hospital

Adelaide, , Australia

Barwon Health

Geelong, , Australia

Western Hospital

Melbourne, , Australia

Medizinische Universität Wien -AKH Wien

Vienna, , Austria

Nuclear Medicine Physician, Jules Bordet Institute

Brussels, , Belgium

University Hospital Gasthuisberg

Leuven, , Belgium

Thunder Bay Regional Health Sciences Centre-Regional Cancer Care

Thunder Bay, Ontario, Canada

Sunnybrook Research Institute

Toronto, Ontario, Canada

CSSS Champlain Charles LeMoyne

Greenfield Park, Quebec, Canada

CHU A Michallon

Grenoble, Cedex 9, France

CHU Dupuytren

Limoges, Cedex, France

CHU Amiens, Hôpital Sud

Amiens, , France

CH Avignon

Avignon, , France

CH de la Côte Basque, Service d'Hématologie

Bayonne, , France

Hématologie - CHU Jean Minjoz

Besançon, , France

Institut Bergonié

Bordeaux, , France

Hopital MORVAN - CHU Brest

Brest, , France

Centre François Baclesse, Comite Hématologie

Caen, , France

Hôpital Henri MONDOR

Créteil, , France

CHD Vendée

La Roche-sur-Yon, , France

CHRU Lille- Hospital Claude Huriez

Lille, , France

Institut Paoli-Calmettes

Marseille, , France

CHR Metz-Thionville

Metz, , France

CH de Mulhouse - Hôpital Emile Muller

Mulhouse, , France

Centre Antoine Lacassagne

Nice, , France

CHR Orléans

Orléans, , France

Institut Curie

Paris, , France

Centre Hospitalier Saint Jean

Perpignan, , France

Hôpital Haut-Levêque Centre F.Magendie

Pessac, , France

Centre Hospitalier René Dubos,

Pontoise, , France

Service d'Hématologie Centre Henri Becquerel

Rouen, , France

CHU de Brabios

Vandœuvre-lès-Nancy, , France

St James 's Hospital

Dublin, , Ireland

University Hospital Galway

Galway, , Ireland

Soroka Medical Centre

Beersheba, , Israel

Rambam Health Care Campus

Haifa, , Israel

Hadassah Medical Organization

Jerusalem, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Tel Aviv Sourasky Medical Centre

Tel Aviv, , Israel

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

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

Bologna, , Italy

New Ematologia dell'Ospedale "Spedali Civili" di Brescia

Brescia, , Italy

Divisione di Ematoncologia

Milan, , Italy

Azienda Ospedaliera Sant'Andrea

Roma, , Italy

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

Torino, , Italy

Meander Medisch Centrum

Amersfoort, , Netherlands

VU Medisch Centrum

Amsterdam, , 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

University Medical Center Radboud Nijmegen

Nijmegen, , Netherlands

Erasmus Medisch Centrum

Rotterdam, , Netherlands

Haga Ziekenhuis

The Hague, , Netherlands

Auxilio Mutuo Cancer Center

San Juan, , Puerto Rico

Clínica Universidad de Navarra (CUN)

Pamplona, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Miguel Servet University Hospital

Zaragoza, , Spain

Department of Haematology Bristol Royal Infirmary

Bristol, , United Kingdom

Poole General Hospital

Dorset, , United Kingdom

Beatson Cancer Centre

Glasgow, , United Kingdom

King's College Hospital

London, , United Kingdom

The Christie NHS Foundation Trust, The Christie Hospital,

Manchester, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; France; Ireland; Israel; Italy; Netherlands; Puerto Rico; Spain; United Kingdom

Other Identifiers

SPI-ZEV-11-301

Identifier Type: -

Identifier Source: org_study_id