Trial Outcomes & Findings for Zevalin (Ibritumomab Tiuxetan) for Early Stage Indolent Lymphomas (NCT NCT00493467)

Last Updated: 2022-09-15

Results Overview

ORR defined as the percentage of number of complete response (CR), complete response unconfirmed (CRu) or partial response (PR) in patients treated using International Working Group (IWG) revised response criteria for Malignant Lymphoma. ORR to therapy is evaluated after three months using radiographic and clinical parameters to assess response. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms. CRu: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameters (SPD). Individual nodes that were previously confluent must have regressed by more than 75% in their SPD compared to the original mass and indeterminate bone marrow. PR: ≥ 50% decrease in SPD of the six largest dominant nodes or nodal masses. No increase in the size of other nodes, liver or spleen and no new sites of disease.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Up to 5 years; Evaluation at 3-month intervals during Year 1, then every 6 months to Year 4. The median follow-up was 56 months for censored observations.

Results posted on

2022-09-15

Participant Flow

Recruitment Period: June 12, 2006 to May 08, 2009. All recruitment was done at The University of Texas (UT) MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure	Zevalin Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of \^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m\^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Overall Study STARTED	31
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Zevalin Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of \^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m\^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Overall Study Death	1

Baseline Characteristics

Zevalin (Ibritumomab Tiuxetan) for Early Stage Indolent Lymphomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zevalin n=31 Participants Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of \^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m\^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Age, Continuous	60 years n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years; Evaluation at 3-month intervals during Year 1, then every 6 months to Year 4. The median follow-up was 56 months for censored observations.

Outcome measures

Outcome measures
Measure	Zevalin n=31 Participants Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of \^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m\^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Overall Response Rate (ORR) Complete Response	67.7 Percentage of Participants
Overall Response Rate (ORR) Complete Response Unconfirmed	29.0 Percentage of Participants
Overall Response Rate (ORR) Partial Response	3.3 Percentage of Participants

SECONDARY outcome

Timeframe: Evaluation at 3-month intervals during the first year and then every 6 months until year 3

PFS measured, in a responder, from the date when a CR, CRu or PR is first noted to the first date at which progressive disease is observed or death. An ongoing PFS interval occurs when there is a responder for whom progressive disease has not been noted. Progression of disease defined as enlargement of liver/spleen, new sites observed, new or increased lymph nodes or lymph node masses, or reappearance of bone marrow.

Outcome measures

Outcome measures
Measure	Zevalin n=31 Participants Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of \^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m\^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Progression Free Survival (PFS) Rate at 3 Years Male	0.62 Proportion of participants Interval 0.4 to 0.95
Progression Free Survival (PFS) Rate at 3 Years Female	0.89 Proportion of participants Interval 0.75 to 1.0

Adverse Events

Zevalin

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Zevalin n=31 participants at risk Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of \^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m\^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Gastrointestinal disorders PERFORATION, GI	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
General disorders DEATH	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.

Other adverse events

Other adverse events
Measure	Zevalin n=31 participants at risk Ibritumomab Tiuxetan (Zevalin): 111In Zevalin (5 mCi of \^111In, 1.6 mg of Ibritumomab Tiuxetan) intravenous (IV) over 10 minutes on Day 1; 90Y Zevalin 0.3 or 0.4 mCi/kg IV over 10 minutes on Day 8. Rituximab: 250 mg/m\^2 IV over 4-6 Hours on Days 1 and 8 prior to the administration of 111In Zevalin and 90Y Zevalin, respectively.
Gastrointestinal disorders ABDOMEN PAIN	6.5% 2/31 • Number of events 2 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Infections and infestations ABDOMINAL INFECTION	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Immune system disorders ALLERGIC REACTION	6.5% 2/31 • Number of events 2 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Immune system disorders ALLERGIC RHINITIS	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Gastrointestinal disorders ANOREXIA	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Infections and infestations BLADDER INFECTION	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Eye disorders BLURRED VISION	12.9% 4/31 • Number of events 4 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Injury, poisoning and procedural complications BRUISING	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Gastrointestinal disorders CONSTIPATION	12.9% 4/31 • Number of events 4 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Gastrointestinal disorders COUGH	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Gastrointestinal disorders DIARRHEA	12.9% 4/31 • Number of events 4 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Nervous system disorders DIZZINESS	12.9% 4/31 • Number of events 4 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Eye disorders DRY EYE	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Respiratory, thoracic and mediastinal disorders DYSPNEA	6.5% 2/31 • Number of events 2 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
General disorders EDEMA: HEAD AND NECK	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
General disorders EDEMA: LIMB	12.9% 4/31 • Number of events 4 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
General disorders FATIGUE	61.3% 19/31 • Number of events 19 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Investigations FEVER WITHOUT NEUTROPHIL INCREASE	12.9% 4/31 • Number of events 4 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Nervous system disorders HEADACHE	9.7% 3/31 • Number of events 3 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Gastrointestinal disorders HEARTBURN	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Investigations HEMOGLOBIN INCREASE	38.7% 12/31 • Number of events 12 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Respiratory, thoracic and mediastinal disorders HEMORRHAGE, PULMONARY	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Infections and infestations INFECTION UNKNOWN	6.5% 2/31 • Number of events 2 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Infections and infestations INFECTION WITHOUT NEUTROPHIL INCREASE	6.5% 2/31 • Number of events 2 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Psychiatric disorders INSOMNIA	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Blood and lymphatic system disorders LEUKOCYTOSIS	61.3% 19/31 • Number of events 19 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Musculoskeletal and connective tissue disorders MUSCLE SPASM	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Gastrointestinal disorders NAUSEA	25.8% 8/31 • Number of events 8 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Nervous system disorders NEUROPATHY: SENSOR	25.8% 8/31 • Number of events 8 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Investigations NEUTROPHILS CHANGE (Absolute neutrophil count (ANC))	67.7% 21/31 • Number of events 21 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
General disorders PAIN	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Gastrointestinal disorders PAIN (ABDOMEN NOS)	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Musculoskeletal and connective tissue disorders PAIN (BACK)	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Nervous system disorders PAIN (HEAD/HEADACHES)	6.5% 2/31 • Number of events 2 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Musculoskeletal and connective tissue disorders PAIN (JOINT)	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Musculoskeletal and connective tissue disorders PAIN (MUSCLE)	9.7% 3/31 • Number of events 3 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Reproductive system and breast disorders PAIN PELVIC	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Gastrointestinal disorders PERFORATION, GI	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Investigations PLATELETS, DECREASE	67.7% 21/31 • Number of events 21 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Eye disorders PROPTOSIS/Enophthalmos	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Skin and subcutaneous tissue disorders PRURITUS	6.5% 2/31 • Number of events 2 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Skin and subcutaneous tissue disorders RASH/DESQUAMATION	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Eye disorders REDNESS OF EYES	6.5% 2/31 • Number of events 2 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
General disorders RIGORS/CHILLS	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
General disorders SWEATING	9.7% 3/31 • Number of events 3 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Vascular disorders THROMBOSIS/THROMBUS	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Eye disorders TINNITUS	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Reproductive system and breast disorders VAGINAL BLEEDING	3.2% 1/31 • Number of events 1 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.
Gastrointestinal disorders VOMITING	9.7% 3/31 • Number of events 3 • Adverse events collected during treatment period including time from first Rituxan infusion (through Day 8) up to 12 weeks following Zevalin infusion.

Additional Information

Felipe Samaniego, MD/Associate Professor, Lymphoma/Myeloma

University of Texas (UT) MD Anderson Cancer Center

Phone: 713-563-1509

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place