Study of Zevalin Versus Observation in Participants at Le... | NCT01510184

NCT01510184

Status Module

Label	Type	Description	Intervention Names
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.

Name	Type	Description	Arm Group Labels	Other Names
Zevalin	Drug	Zevalin administered intravenous infusion.	Zevalin	Ibritumomab Tiuxetan

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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)
Overall Survival Rate at 24 Months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Facility	Status	City	State	ZIP	Country	Contacts
Cancer Treatment Services Arizona		Casa Grande	Arizona	85122	United States
Sutter East Bay Hospitals

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment. Overall number of participants analyzed signifies participants who were alive.

Posted

Median

Full Range

months

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

ID	Title	Description
OG000	Zevalin	Participants received rituximab 250 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 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 mCi/kg 10-minute intravenous push (0.3 mCi/kg in participants with a platelet count in 100,000/μL to 149,000/μL).
OG001	Observation	Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease

Units	Counts
Participants	OG00035 OG00141

Title

Denominators

Categories

Title	Measurements
	OG0008.90(2.73 to 22.60) OG0016.14(0.07 to 21.32)

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.

Posted

Median

Full Range

months

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

ID	Title	Description
OG000	Zevalin	Participants received rituximab 250 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 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 mCi/kg 10-minute intravenous push (0.3 mCi/kg in participants with a platelet count in 100,000/μL to 149,000/μL).
OG001	Observation	Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease

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.

Data for this outcome measure was not collected and analyzed due to early termination of study for sponsor business decision.

Posted

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

ID	Title	Description
OG000	Zevalin	Participants received rituximab 250 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 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 mCi/kg 10-minute intravenous push (0.3 mCi/kg in participants with a platelet count in 100,000/μL to 149,000/μL).
OG001	Observation	Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease

Units	Counts
Participants

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.

Data for this outcome measure was not collected and analyzed due to early termination of study for sponsor business decision.

Posted

24 Months

ID	Title	Description
OG000	Zevalin	Participants received rituximab 250 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 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 mCi/kg 10-minute intravenous push (0.3 mCi/kg in participants with a platelet count in 100,000/μL to 149,000/μL).
OG001	Observation	Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0004 affected36 at risk EG0011 affected43 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0002 affected36 at risk EG0010 affected43 at risk
Leukopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected36 at risk EG0010 affected43 at risk
Death	General disorders	Systematic Assessment	EG0000 affected36 at risk EG0012 affected43 at risk
Lung infection	Infections and infestations	Systematic Assessment	EG0001 affected36 at risk EG0010 affected43 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0002 affected36 at risk EG0010 affected43 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment	EG0001 affected36 at risk EG0010 affected43 at risk
Syncope	Nervous system disorders	Systematic Assessment	EG0001 affected36 at risk EG0010 affected43 at risk
Depressed level of consciousness	Nervous system disorders	Systematic Assessment	EG0000 affected36 at risk EG0011 affected43 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0001 affected36 at risk EG0010 affected43 at risk
Embolism	Vascular disorders	Systematic Assessment	EG0000 affected36 at risk EG0011 affected43 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0006 affected36 at risk EG0010 affected43 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0006 affected36 at risk EG0011 affected43 at risk
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG0005 affected36 at risk EG0010 affected43 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0005 affected36 at risk EG0010 affected43 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0004 affected36 at risk EG0011 affected43 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0003 affected36 at risk EG0013 affected43 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0002 affected36 at risk EG0010 affected43 at risk
Fatigue	General disorders	Systematic Assessment	EG00010 affected36 at risk EG0012 affected43 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0006 affected36 at risk EG0010 affected43 at risk
Neutrophil count decreased	Investigations	Systematic Assessment	EG0006 affected36 at risk EG0010 affected43 at risk
White blood cell count decreased	Investigations	Systematic Assessment	EG0006 affected36 at risk EG0010 affected43 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment	EG0004 affected36 at risk EG0010 affected43 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0003 affected36 at risk EG0010 affected43 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 affected36 at risk EG0012 affected43 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0003 affected36 at risk EG0010 affected43 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0002 affected36 at risk EG0011 affected43 at risk
Dysgeusia	Nervous system disorders	Systematic Assessment	EG0002 affected36 at risk EG0010 affected43 at risk
Neuropathy peripheral	Nervous system disorders	Systematic Assessment	EG0000 affected36 at risk EG0013 affected43 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 affected36 at risk EG0010 affected43 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 affected36 at risk EG0010 affected43 at risk

ID	Term
D016403	Lymphoma, Large B-Cell, Diffuse
D008224	Lymphoma, Follicular

ID	Term
D016393	Lymphoma, B-Cell
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Zevalin	Participants received rituximab 250 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 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 mCi/kg 10-minute intravenous push (0.3 mCi/kg in participants with a platelet count in 100,000/μL to 149,000/μL).
BG001	Observation	Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Zevalin	Participants received rituximab 250 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 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 mCi/kg 10-minute intravenous push (0.3 mCi/kg in participants with a platelet count in 100,000/μL to 149,000/μL).	1	36	8	36	21	36
EG001	Observation	Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease	2	43	3	43	7	43