Trial Outcomes & Findings for 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 NCT01510184)

Last Updated: 2021-12-16

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

79 participants

Primary outcome timeframe

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

Results posted on

2021-12-16

Participant Flow

A total of 79 participants were enrolled into the study from 19 Apr 2012 to 23 Oct 2014.

Participant milestones

Participant milestones
Measure	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).	Observation Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease
Overall Study STARTED	36	43
Overall Study COMPLETED	6	8
Overall Study NOT COMPLETED	30	35

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	Observation Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease
Overall Study Sponsor discretion	28	28
Overall Study Death	1	2
Overall Study Withdrawal by Subject	1	4
Overall Study Other	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zevalin n=36 Participants 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).	Observation n=43 Participants Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease	Total n=79 Participants Total of all reporting groups
Age, Continuous	69 years STANDARD_DEVIATION 1.02 • n=5 Participants	71 years STANDARD_DEVIATION 1.06 • n=7 Participants	70 years STANDARD_DEVIATION 0.75 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	21 Participants n=7 Participants	37 Participants n=5 Participants

PRIMARY outcome

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

Population: 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.

Outcome measures

Outcome measures
Measure	Zevalin n=35 Participants 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).	Observation n=41 Participants Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease
Overall Survival (OS) for Living Participants	8.90 months Interval 2.73 to 22.6	6.14 months Interval 0.07 to 21.32

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Zevalin n=1 Participants 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).	Observation n=2 Participants Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease
Overall Survival for Death	16.76 months Interval 16.76 to 16.76	5.82 months Interval 1.94 to 9.69

SECONDARY outcome

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

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

PFS was defined as the time interval between the date of randomization and the date of relapse or death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 Months

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

The OS rate at 24-month defined as the percentage of all randomized participants who died within 24 months of randomization.

Outcome measures

Outcome data not reported

Adverse Events

Zevalin

Serious events: 8 serious events

Other events: 21 other events

Deaths: 1 deaths

Observation

Serious events: 3 serious events

Other events: 7 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Zevalin n=36 participants at risk 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).	Observation n=43 participants at risk Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease
Blood and lymphatic system disorders Neutropenia	11.1% 4/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	2.3% 1/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Blood and lymphatic system disorders Thrombocytopenia	5.6% 2/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Blood and lymphatic system disorders Leukopenia	2.8% 1/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
General disorders Death	0.00% 0/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	4.7% 2/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Infections and infestations Lung infection	2.8% 1/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Investigations Platelet count decreased	5.6% 2/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Investigations Lymphocyte count decreased	2.8% 1/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Nervous system disorders Syncope	2.8% 1/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Nervous system disorders Depressed level of consciousness	0.00% 0/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	2.3% 1/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Vascular disorders Hypotension	2.8% 1/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Vascular disorders Embolism	0.00% 0/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	2.3% 1/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.

Other adverse events

Additional Information

Gajanan Bhat, PhD

Spectrum Pharmaceuticals

Phone: 949-743-9219

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Zevalin n=36 participants at risk 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).	Observation n=43 participants at risk Participants who were randomized in this arm group did not receive any anti-lymphoma therapy unless they had a relapse of their disease
Blood and lymphatic system disorders Thrombocytopenia	16.7% 6/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Blood and lymphatic system disorders Neutropenia	16.7% 6/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	2.3% 1/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Blood and lymphatic system disorders Anaemia	13.9% 5/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Gastrointestinal disorders Constipation	13.9% 5/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Gastrointestinal disorders Nausea	11.1% 4/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	2.3% 1/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Gastrointestinal disorders Diarrhoea	8.3% 3/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	7.0% 3/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Gastrointestinal disorders Vomiting	5.6% 2/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
General disorders Fatigue	27.8% 10/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	4.7% 2/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Investigations Platelet count decreased	16.7% 6/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Investigations Neutrophil count decreased	16.7% 6/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Investigations White blood cell count decreased	16.7% 6/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Investigations Lymphocyte count decreased	11.1% 4/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Musculoskeletal and connective tissue disorders Back pain	8.3% 3/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 2/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	4.7% 2/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Nervous system disorders Headache	8.3% 3/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Nervous system disorders Dizziness	5.6% 2/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	2.3% 1/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Nervous system disorders Dysgeusia	5.6% 2/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Nervous system disorders Neuropathy peripheral	0.00% 0/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	7.0% 3/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 3/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Skin and subcutaneous tissue disorders Pruritus	5.6% 2/36 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/43 • From first dose up to approximately 2.5 years Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.