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

Diffuse Large B-cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01510184
• Other study ID #: SPI-ZEV-11-301
• Status: Terminated
• Phase: Phase 3
• Start date: April 19, 2012
• Est. completion date: October 23, 2014

Study information

• Verified date: November 2021
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 79
• Est. completion date: October 23, 2014
• Est. primary completion date: October 23, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Follicle Center Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Zevalin
Zevalin administered intravenous infusion.
• Y-90-Zevalin
Y-90-Zevalin administered by intravenous infusion.
• Rituximab
Rituximab administered by intravenous infusion.
• In-111 Zevalin
In-111-Zevalin administered by intravenously.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Barwon Health	Geelong
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Western Hospital	Melbourne
Australia	Royal Melbourne	Parkville	Victoria
Austria	Medizinische Universität Wien -AKH Wien	Vienna
Belgium	Nuclear Medicine Physician, Jules Bordet Institute	Bruxelles
Belgium	University Hospital Gasthuisberg	Leuven
Canada	CSSS Champlain Charles LeMoyne	Greenfield Park	Quebec
Canada	Thunder Bay Regional Health Sciences Centre-Regional Cancer Care	Thunder Bay	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario
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	Besancon
France	Institut Bergonié	Bordeaux
France	Hopital MORVAN - CHU Brest	Brest
France	Centre François Baclesse, Comite Hématologie	Caen
France	Hôpital Henri MONDOR	Creteil
France	CHU A Michallon	Grenoble	Cedex 9
France	CHD Vendée	La Roche-sur-Yon
France	CHRU Lille- Hospital Claude Huriez	Lille
France	CHU Dupuytren	Limoges	Cedex
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	Orleans
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	Vandoeuvre-les-nancy
Ireland	St James 's Hospital	Dublin
Ireland	University Hospital Galway	Galway
Israel	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-Hashomer
Italy	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	Milano
Italy	Azienda Ospedaliera Sant'Andrea	Roma
Italy	Azienda Ospedaliera San. Giovanni Battista di Torino, Dipartimento di Oncologia U.O.A Ematologia, Le Molinette,	Torino
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	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	University Medical Center Radboud Nijmegen	Nijmegen
Netherlands	Erasmus Medisch Centrum	Rotterdam
Puerto Rico	Auxilio Mutuo Cancer Center	San Juan
Spain	Clínica Universidad de Navarra (CUN)	Pamplona
Spain	Hospital Universitario Miguel Servet	Zaragoza
Spain	Miguel Servet University Hospital	Zaragoza
United Kingdom	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 States	Piedmont Hospital Cancer Center	Atlanta	Georgia
United States	Sutter East Bay Hospitals	Berkeley	California
United States	St. Luke's Mountain States Tumor Institute (MSTI)	Boise	Idaho
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Cancer Treatment Services Arizona	Casa Grande	Arizona
United States	Associates In Oncology and Hematology	Chattanooga	Tennessee
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Halifax Health Medical Center	Daytona Beach	Florida
United States	Decatur Memorial Hospital Cancer Care Specialists of Central Illinois	Decatur	Illinois
United States	City of Hope	Duarte	California
United States	Adams Cancer center	Gettysburg	Pennsylvania
United States	Saint Francis Hospital	Greenville	South Carolina
United States	St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Hackensack UMC / John Theurer Cancer Center	Hackensack	New Jersey
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	The University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Norton Cancer Institute, Suburban	Louisville	Kentucky
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Illinois Cancer Specialists	Niles	Illinois
United States	Saint Louis University	Saint Louis	Missouri
United States	Oncology Research-Park Nicollet Institute	Saint Louis Park	Minnesota
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Avera Hematology and Transplant	Sioux Falls	South Dakota
United States	H. Lee Moffitt Cancer Center	Tampa	Florida
United States	York Cancer Center / Cancer Care Associates of York	York	Pennsylvania
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Progression-Free Survival (PFS)	PFS was defined as the time interval between the date of randomization and the date of relapse or death from any cause.	From randomization till death or end of study, whichever occurs first (Up to approximately 2.5 years)
Secondary	Overall Survival Rate at 24 Months	The OS rate at 24-month defined as the percentage of all randomized participants who died within 24 months of randomization.	24 Months